POPULARITY
3 episodes with sirt1
2 episodes with sirt1
5 episodes with sirt1
2 episodes with sirt1
2 episodes with sirt1
2 episodes with sirt1
2 episodes with sirt1
2 episodes with sirt1
2 episodes with sirt1
Request Access to the FREE Health Impact SoftwareClick this link. FREE Health Impact APPNo strings attached—we will send an email, and you'll receive an exclusive download link.Take Action:
Could NAD+ be the key to living longer and healthier? In this episode, Nurse Doza breaks down the science behind NAD+, its role in mitochondrial function, and the differences between oral and IV NAD+ supplementation. Discover how NAD+ impacts aging, energy levels, and overall health—and whether IV therapy is truly the most effective way to boost your NAD+ levels. 5 Key Takeaways NAD+ is essential for cellular energy and longevity. It plays a critical role in mitochondrial function, metabolism, and overall health. IV NAD+ provides faster and more effective absorption. Studies suggest that IV administration leads to a rapid and complete tissue uptake compared to oral forms. Oral NAD+ supplements rely on precursors. While supplements like NMN and NR can increase NAD+ levels, they may not be as effective as direct NAD+ infusions. NAD+ plays a role in addiction recovery. IV NAD+ has been used in protocols for substance withdrawal, potentially reducing cravings and withdrawal symptoms. Resveratrol and other compounds support NAD+ metabolism. Certain antioxidants, like resveratrol, help regulate inflammation and mitochondrial biogenesis. Featured Product: Mitochondriac Mitochondriac is designed to fuel your mitochondria, supporting energy production and longevity—key benefits linked to NAD+ optimization. By enhancing cellular health, Mitochondriac complements the insights shared in this episode on how NAD+ impacts overall vitality. Timestamps 00:00 START 03:15 What is NAD+ and why does it matter? 08:45 How NAD+ affects mitochondrial function and energy levels 14:30 Differences between oral and IV NAD+ supplementation 21:10 Scientific research on NAD+ absorption and metabolism 28:50 The role of NAD+ in addiction recovery and brain health 36:25 How NAD+ impacts inflammation and oxidative stress 42:40 Resveratrol, SIRT1 activation, and mitochondrial biogenesis 50:15 NAD+, longevity, and anti-aging strategies 57:00 Final thoughts and practical takeaways Resources Mentioned Study on NAD+ absorption and tissue uptake Study on IV NAD+ for addiction recovery Resveratrol's role in mitochondrial health NAD+ and addiction research Study on NAD+ metabolism in viral infections
Send me a text!Food plays a remarkable role in healing, but the timing of when we eat or abstain can significantly affect our health as well. Fasting serves as a powerful tool to support longevity. It not only triggers the activation of anti-aging genes but also strengthens the immune system by repairing damaged DNA and eliminating compromised cells. Fasting has also been shown to enhance metabolic flexibility, sharpen mental focus, and support consistent energy levels. Today I'm joined by Cynthia Thurlow, NP, the CEO and founder of the Everyday Wellness Project, and international speaker, with over 10 million views for her second TEDx talk (Intermittent Fasting: Transformational Technique). With over 20 years of experience in health and wellness, Cynthia is a globally recognized expert in intermittent fasting and nutritional health, and has been featured on ABC, FOX5, and Entrepreneur among others. Cynthia hosts the Everyday Wellness podcast, considered one of "21 Podcasts To Expand Your Mind in 2021” by Business Insider. Her mission is to educate women on the benefits of intermittent fasting and overall holistic health and wellness, so they feel empowered to live their most optimal lives. In this episode, Cynthia and I discuss the benefits of intermittent fasting – from longevity to metabolic health to cognitive functioning, how to fast correctly, who should & shouldn't be fasting, the optimal meal to break a fast, and so much more. Suggested Resources:Cynthia Thurlow | Website | InstagramIntermittent Fasting Transformation: The 45-Day Program for Women to Lose Stubborn Weight, Improve Hormonal Health, and Slow AgingCalorie Restriction with or without Time-Restricted Eating in Weight LossBeneficial Effects of Early Time-Restricted Feeding on Metabolic Diseases: Importance of Aligning Food Habits with the Circadian ClockFasting promotes the expression of SIRT1, an NAD+ -dependent protein deacetylaseHow To Fast and Eat During Different Stages Of Your CycleQualia Senolytic combines 9 vegan, plant-derived compounds to help your body naturally eliminate zombie (or senescent) cells, that help us age better at the cellular level so we can feel YEARS younger! Use the code WELLNSTRONG for 15% off!Join the WellnStrong mailing list for exclusive content here!Want more of The How To Be WellnStrong Podcast? Subscribe to the YouTube channel. Follow Jacqueline: Instagram Pinterest TikTok Youtube To access notes from the show & full transcripts, head over to WellnStrong's Podcast Page
Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: A primer on the current state of longevity research, published by Abhishaike Mahajan on August 22, 2024 on LessWrong. Note: This post is co-authored with Stacy Li, a PhD student at Berkeley studying aging biology! Highly appreciate all her help in writing, editing, and fact-checking my understanding! Introduction The last time I read about aging research deeply was around 2021. The general impression I was getting was that aging research was increasingly more and more funded (good!). Unfortunately, none of the money led to actionable or useful insights (bad). Over time, you get slightly burnt out by all the negative news. After getting a job in biotech, I kept a hazy eye on the subject but mostly tuned out of it entirely. But, especially today, I am curious: how has the aging field progressed in the last few years? Since 2021, what has changed? In this post, I'll share a list of immediate questions about the state of affairs in aging research, and the answers I've found for them. For each question, I'll offer some basic background knowledge required to understand the question. Feel free to skip that part if you already understand the question! Did the therapeutic focus on sirtuins amount to much? Background Sirtuins are a family of signaling proteins, commonly referred to by their corresponding gene name, SIRT1, SIRT2, all the way up to SIRT7. Their primary role is deacetylation, which is just the removal of a chemical marker (acetyl) on proteins. It was noticed in the 1980s that some sirtuin classes were especially involved in three key activities: modifying histones, which are proteins that tune the accessibility of DNA in the nucleus, transcriptional modification, which determines how DNA is interpreted by the body, and DNA repair, which speaks for itself. And anything involved in modifying and maintaining DNA is something worth paying attention to! Studies in the 2000s showed that the activity of specific sirtuin classes strongly correlated with age; the young had more sirtuin activity, and the old had less. This seemed to be causative in aging; overexpressing certain sirtuin genes led to lifespan increase and downregulation of them led to lifespan decrease. The results were a bit mixed, and the results were for yeast cells - always a red flag - but there was some promise in viewing sirtuins as an aging target. It turns out that editing humans to safely overexpress sirtuin genes is somewhat hard to do (as is expressing any gene in humans). But there was an easy way around that: focus on molecules that are required for sirtuin to do its job. A class of therapeutics grew from this: sirtuin-activating compounds. How do you activate sirtuins? Well, sirtuins are dependent on NAD+, or nicotinamide adenine dinucleotide, to perform their primary function. Increasing cellular NAD+ levels could also be a way to indirectly push for more sirtuin activity. Practically speaking, NAD+ bioavailability is poor, so supplementation with precursors to NAD+, such as nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), was instead used. There are plenty of other compounds in this category too: resveratrol, fisetin, and quercetin are all names you may hear mentioned. How has this fared? Answer TLDR: The whole sirtuin theory was losing steam by the time I started reading about it a few years ago. It's only gotten worse. Nothing particularly useful has come from sirtuin-focused therapies, and likely nothing ever will. A Cell paper from 2018 found that NAD+ precursor supplementation didn't improve mice longevity. To be fair, they did show that supplementation improves some aspects of health-span, specifically improved glucose metabolism and reduced oxidative stress to the liver in aged mice, so still potentially useful. But nothing revolutionary. Still, human clinical trials ...
Link to original articleWelcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: A primer on the current state of longevity research, published by Abhishaike Mahajan on August 22, 2024 on LessWrong. Note: This post is co-authored with Stacy Li, a PhD student at Berkeley studying aging biology! Highly appreciate all her help in writing, editing, and fact-checking my understanding! Introduction The last time I read about aging research deeply was around 2021. The general impression I was getting was that aging research was increasingly more and more funded (good!). Unfortunately, none of the money led to actionable or useful insights (bad). Over time, you get slightly burnt out by all the negative news. After getting a job in biotech, I kept a hazy eye on the subject but mostly tuned out of it entirely. But, especially today, I am curious: how has the aging field progressed in the last few years? Since 2021, what has changed? In this post, I'll share a list of immediate questions about the state of affairs in aging research, and the answers I've found for them. For each question, I'll offer some basic background knowledge required to understand the question. Feel free to skip that part if you already understand the question! Did the therapeutic focus on sirtuins amount to much? Background Sirtuins are a family of signaling proteins, commonly referred to by their corresponding gene name, SIRT1, SIRT2, all the way up to SIRT7. Their primary role is deacetylation, which is just the removal of a chemical marker (acetyl) on proteins. It was noticed in the 1980s that some sirtuin classes were especially involved in three key activities: modifying histones, which are proteins that tune the accessibility of DNA in the nucleus, transcriptional modification, which determines how DNA is interpreted by the body, and DNA repair, which speaks for itself. And anything involved in modifying and maintaining DNA is something worth paying attention to! Studies in the 2000s showed that the activity of specific sirtuin classes strongly correlated with age; the young had more sirtuin activity, and the old had less. This seemed to be causative in aging; overexpressing certain sirtuin genes led to lifespan increase and downregulation of them led to lifespan decrease. The results were a bit mixed, and the results were for yeast cells - always a red flag - but there was some promise in viewing sirtuins as an aging target. It turns out that editing humans to safely overexpress sirtuin genes is somewhat hard to do (as is expressing any gene in humans). But there was an easy way around that: focus on molecules that are required for sirtuin to do its job. A class of therapeutics grew from this: sirtuin-activating compounds. How do you activate sirtuins? Well, sirtuins are dependent on NAD+, or nicotinamide adenine dinucleotide, to perform their primary function. Increasing cellular NAD+ levels could also be a way to indirectly push for more sirtuin activity. Practically speaking, NAD+ bioavailability is poor, so supplementation with precursors to NAD+, such as nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), was instead used. There are plenty of other compounds in this category too: resveratrol, fisetin, and quercetin are all names you may hear mentioned. How has this fared? Answer TLDR: The whole sirtuin theory was losing steam by the time I started reading about it a few years ago. It's only gotten worse. Nothing particularly useful has come from sirtuin-focused therapies, and likely nothing ever will. A Cell paper from 2018 found that NAD+ precursor supplementation didn't improve mice longevity. To be fair, they did show that supplementation improves some aspects of health-span, specifically improved glucose metabolism and reduced oxidative stress to the liver in aged mice, so still potentially useful. But nothing revolutionary. Still, human clinical trials ...
How effective is red light therapy for reducing stress when you irradiate both your brain and your gut?Can methylene blue reduce mortality in those critically ill?How safe and effect is C60 according to a recent toxicity report?In today's solosode, we're diving back into the research! And it ended up being a sheer coincidence that we're covering each topic of The Mitochondrial Triad. The first article looks at how beneficial photobiomodulation can be for reducing stress when you target both the brain and the gut to enhance mental health via the gut-brain axis. The second article is an abstract of a meta-analysis of randomized controlled trials that demonstrates the efficacy and safety of methylene blue for critically ill individuals and perioperative patients. The last study comes from our friends at SES Research where they are studying the toxicity of carbon 60 to verify its safety and efficacy. With C60 being such a new supplement for human consumption, SES Research is going through the necessary and proper steps to demonstrate the safety of this novel and seemingly beneficial molecule. Hopefully, studies like this will help C60 become more widely adopted so that more people can benefit from it. If you found the information in today's episode particularly interesting and/or compelling, please share it with a family member, friend, colleague and/or anyone that you think could benefit and be illuminated by this knowledge. Sharing is caring :)As always, light up your health! - Key points: Product Announcement - 00:01:26 - 00:02:11 Summer in Montana and Outdoor Activities - 00:02:11 - 00:03:04 Red Light Therapy for Mitochondrial and Mental Health - 00:03:04 - 00:04:08 Brain-Gut Photobiomodulation and Stress-Induced Cognitive Changes - 00:04:08 - 00:07:29 Combining Brain and Gut Photobiomodulation - 00:07:29 - 00:08:50 Regular Red Light Therapy for Enhanced Health - 00:08:50 - 00:12:27 Full Body Devices and Systemic Treatment - 00:16:42 - 00:17:45 Photobiomodulation Benefits and Disease Prevention - 00:17:45 - 00:21:24 Methylene Blue for Critically Ill Patients - 00:22:14 - 00:27:56 Introduction to C60 (Carbon 60) - 00:27:56 - 00:31:27 Safety Studies on Pure C60 - 00:31:27 - 00:33:44 Recent Study on C60 in Rats - 00:33:44 - 00:37:18 Importance of High-Quality C60 Products - 00:37:18 - 00:42:42 Testing and Benefits of High-Purity C60 - 00:42:42 - 00:48:54 - Articles referenced in episode: Brain–gut photobiomodulation restores cognitive alterations in chronically stressed mice through the regulation of Sirt1 and neuroinflammation Methylene Blue Reduces Mortality in Critically Ill and Perioperative Patients: A Meta-Analysis of Randomized Trials A regulatory compliant short-term oral toxicity study of soluble [60]fullerenes in rats - Check out BioLight's two most popular Bundles!1.) The Mitochondrial Triad Bundle: For this bundle, you choose one of each: one BioBlue product, one BioC60 product and one red light therapy product and save 20% on the entire order! 2.) The BioBundle: For this bundle, choose your favorite BioBlue product and your favorite BioC60 product and save 15%! You can save an additional 10% buy subscribing to this bundle. That's correct, you can save a total of 25% via the BioBundle! - To learn more about red light therapy and shop for the highest-quality red light therapy, methylene blue & C60 products, visit https://www.biolight.shop - Dr. Mike's #1 recommendations: Water products: Water & Wellness Grounding products: Earthing.com EMF-mitigating products: Somavedic Blue light-blocking glasses: Ra Optics - Stay up-to-date on social media: Dr. Mike Belkowski: Instagram LinkedIn BioLight: Website Instagram YouTube Facebook
A review of the laters mental health news. We'll discover a controversial way of treating addiction and Mexico is the example. Let's Connect --> https://drmatmonharrell.bio.link/Episode written by Dr. Matmon HarrellMusic provided by PodcastleReferencesGarcia A, Anderson B. Violence, addiction, recovery: An anthropological study of Mexico's anexos. Transcult Psychiatry. 2016 Aug;53(4):445-64. doi: 10.1177/1363461516662539. Epub 2016 Aug 17. PMID: 27535824; PMCID: PMC5531188.Molzahn C, Rodriguez Ferreira O, Shirk D. Drug violence in Mexico: Data and analysis through 2012. Transborder Institute, University of San Diego; 2013. Retrieved from https://justiceinmexico.files.wordpress.com/2013/02/130206-dvm-2013-final.pdf. [Google Scholar] [Ref list]United Nations Office on Drugs and Crime. World drug report 2014. Author; 2014. Retrieved from https://www.unodc.org/documents/data-and-analysis/WDR2014/World_Drug_Report_2014_web.pdf. [Google Scholar] [Ref list]Ackerman, D., & Chakrabarti, M. (2024). Underground addiction care in mexico - and its spread to the U.S. NPR. https://www.wbur.org/onpoint/2024/04/29/underground-addiction-care-mexico-rehab Anna Sancho-Balsells, Sara Borràs-Pernas, Francesca Flotta, Wanqi Chen, Daniel del Toro, Manuel J. Rodríguez, Jordi Alberch, Guillaume Blivet, Jacques Touchon, Xavier Xifró, Albert Giralt. Brain–gut photobiomodulation restores cognitive alterations in chronically stressed mice through the regulation of Sirt1 and neuroinflammation. Journal of Affective Disorders, 2024; 354: 574 DOI: 10.1016/j.jad.2024.03.075University of Barcelona. (2024, May 2). Low intensity light to fight the effects of chronic stress. ScienceDaily. Retrieved May 4, 2024 from www.sciencedaily.com/releases/2024/05/240502141226.htmBrian L. Edlow, Mark Olchanyi, Holly J. Freeman, Jian Li, Chiara Maffei, Samuel B. Snider, Lilla Zöllei, J. Eugenio Iglesias, Jean Augustinack, Yelena G. Bodien, Robin L. Haynes, Douglas N. Greve, Bram R. Diamond, Allison Stevens, Joseph T. Giacino, Christophe Destrieux, Andre van der Kouwe, Emery N. Brown, Rebecca D. Folkerth, Bruce Fischl, Hannah C. Kinney. Multimodal MRI reveals brainstem connections that sustain wakefulness in human consciousness. Science Translational Medicine, 2024; 16 (745) DOI: 10.1126/scitranslmed.adj4303Massachusetts General Hospital. (2024, May 1). Brain imaging study reveals connections critical to human consciousness. ScienceDaily. Retrieved May 4, 2024 from www.sciencedaily.com/releases/2024/05/240501152947.htm Become a member at https://plus.acast.com/s/themindfulpharmd. Hosted on Acast. See acast.com/privacy for more information.
It seems that methylene blue (MB) has continued to capture the attention on those looking to optimize mitochondrial health — and for good reason. After all, it may be one of the easiest and fastest way to improve mitochondrial function. But remember that third pillar of The Mitochondrial Triad? Yeah, that C60 thing... Perhaps it hasn't gotten as much love on this podcast and/or may be even lesser known than MB. But trust me when I say that C60 is second place to no one when it comes to optimizing cellular energy and mitochondrial function, which, ultimately leads to efficient energy and biological water production.In today's episode, I want to take a deeper dive into C60 and discuss the science of how it can contribute to mitigating diseases while also markedly boosting healthspan and longevity. For that, we'll be reviewing some of Chris Campbell's book, C60 Science: The God Molecule Hypothesis. Quite the book title, right? But the theory posited by Chris it quite intriguing. Needless to say, after this discussion you will see why C60 earned its spot in The Mitochondrial Triad and should be highly considered for anyone that has a mitochondrion in their body.For the red light therapy side of things, I review an ahead of print photobiomodulation research article (it doesn't get officially published until June!) that looks at treating the gut and brain to help reduce chronic stress. The study produced positive results, including: "combined non-invasive photobiomodulation partially restores some gut microbiota dysbiosis induced by chronic stress." Combine this with the vagus nerve treatment via RLT that we learned last week from Abe and we have another triad — this one being a triad of RLT locations to help reduce stress. Non-invasive and non-pharmacological. What's not to like! If you found the information in today's episode particularly interesting and/or compelling, please share it with a family member, friend, colleague and/or anyone that you think could benefit and be illuminated by this knowledge. Sharing is caring :)As always, light up your health! - Key points: Introduction to "The Red Light Report" by Dr. Mike Belkowski. [00:00:00 - 00:00:23] Recap of previous episode, including Abe's insights on pain management. [00:00:23 - 00:02:27] Announcement of upcoming product releases from BioLight in May. [00:02:27 - 00:03:33] Introduction to "C60 Science: The God Molecule Hypothesis" by Chris Campbell. [00:03:33 - 00:04:19] Discussion on C60's role in origins of life and carrier properties. [00:04:19 - 00:06:16] Transition to second chapter, comparing methylene blue and red light therapy benefits. [00:07:12 - 00:08:02] Continuation of discussion on potential benefits of C60. [00:10:47 - 00:25:13] Introduction of the "mitochondrial triad" concept. [00:25:43 - 00:26:16] Plans to create episodes featuring real-life testimonials of the mitochondrial triad's effects. [00:26:16 - 00:32:24] Emphasis on fostering open and honest dialogue within the community. [00:34:27 - 00:36:18] Conclusion: Positive biological effects observed for different brain maladies. [00:37:18 - 00:37:51] Photobiomodulation offers potential therapeutic benefits. [00:41:11 - 00:42:07] Discussion on red light therapy's efficacy, technical details, and therapeutic potential. [00:44:31 - 00:45:31] Emphasis on non-pharmacological strategies and encouragement for research. [00:45:31 - 00:50:22] - Book referenced in episode:C60 Science: The God Molecule Hypothesis, Chris Campbell Article referenced: Brain–gut photobiomodulation restores cognitive alterations in chronically stressed mice through the regulation of Sirt1 and neuroinflammation - Introducing the Red Light Therapy Treatment Protocols Ecosystem! - Don't forget to check out BioLight's two most popular Bundles!1.) The Mitochondrial Triad Bundle For this bundle, you choose one of each: one BioBlue product, one BioC60 product and one red light therapy product and save 20% on the entire order! Click here to check it out. 2.) The BioBundle For this bundle, choose your favorite BioBlue product and your favorite BioC60 product and save 15%!You can save an additional 10% buy subscribing to this bundle.That's correct, you can save a total of 25% via the BioBundle! Click here to check it out. - To learn more about red light therapy and shop for the highest-quality red light therapy products, visit https://www.biolight.shop - Dr. Mike's #1 recommendations: Grounding products: Earthing.com EMF-mitigating products: Somavedic Blue light-blocking glasses: Ra Optics - Stay up-to-date on social media: Dr. Mike Belkowski: Instagram LinkedIn BioLight: Website Instagram YouTube Facebook
What do you really know about the theory of aging? In this episode of the Biohacking Superhuman Performance podcast, we chat with Dr. Sandra Kaufman about the critical functions of SIRT1 and SIRT3 in our bodies, spotlighting how these proteins are not only gatekeepers of DNA repair and mitochondrial efficiency but also promising targets in the quest to combat aging. We dissect the intricacies of supplement bioavailability, pitting resveratrol against its molecular cousin pterostilbene. Dr. Kaufman demystifies recent findings and navigates us through state-of-the-art delivery methods that are revolutionizing the way our bodies absorb these longevity-boosting substances. Adding to the mix, we'll explore the vital role of SIRT1 activation and the myriad factors that contribute to mitochondrial health, reinforcing why this cellular powerhouse is synonymous with our overall well-being. To cap off our enlightening discussion, we delve into the tangible impacts of diet and supplementation on maintaining youthful vitality. Dr. Kaufman shares her candid experiences—from the acquired tastes of traditional Chinese medicine teas to the powerful effects of fucoidan—and offers sage advice on sourcing quality products without breaking the bank. Dr. Kaufmann began her academic career in the field of cellular biology, earning a Master's Degree from the University of Connecticut in Tropical Ecology and Plant Physiology. Turning to medicine, she received her medical Degree at the University of Maryland, and completed a residency and fellowship at Johns Hopkins in the field of pediatric anesthesiology. For the last five years she has been the Chief of Pediatric Anesthesia at the Joe DiMaggio Children's Hospital. Her avid interest in the science of anti-aging began many years ago as an intense hobby. Utilizing her knowledge in cell biology, human pharmacology and physiology, this hobby has now become a main focus. The project represents years of non-clinical research leading to the first, ever, comprehensive theory of aging. What we discuss: (00:02) - Exploring Sirtuins (10:26) - Bioavailability and Activators for CERT1/3 (21:28) - Discussion on Foods and Supplements (33:33) - Cellular Homeostasis and NAD (40:02) - Cellbex and Heat Shock Proteins (53:44) - Exploring Exosomes and Future Clinic Thank you to our sponsors for making this episode possible: Sensate: Go to https://www.getsensate.com and use code NAT Beam Minerals: Go to https://www.beamminerals.com and use code Nathalie to get 20% off your order Profound Health: Visit www.profound-health.com and use code longevity15 to save 15% Find more from Nathalie: YouTube: https://www.youtube.com/channel/UCmholC48MqRC50UffIZOMOQ Facebook Group: https://www.facebook.com/groups/biohackingsuperhumanperformance Instagram: https://www.instagram.com/nathalieniddam/ Website: NatNiddam.com Join Nat's Membership Community: https://www.natniddam.com/bsp-community Work with Nat: Book Your 20 Minute Optimization Consult: https://calendly.com/nniddam/intro-call?month=2021-08 Find more from Dr. Kaufmann: Website: https://kaufmannprotocol.com/ Instagram: https://www.instagram.com/kaufmannantiaging/
BUFFALO, NY- December 27, 2023 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 23, entitled, “Angelica gigas extract inhibits acetylation of eNOS via IRE1α sulfonation/RIDD-SIRT1-mediated posttranslational modification in vascular dysfunction.” Angelica gigas NAKAI (AG) is a popular traditional medicinal herb widely used to treat dyslipidemia owing to its antioxidant activity. Vascular disease is intimately linked to obesity-induced metabolic syndrome, and AG extract (AGE) shows beneficial effects on obesity-associated vascular dysfunction. However, the effectiveness of AGE against obesity and its underlying mechanisms have not yet been extensively investigated. In this new study, researchers Geum-Hwa Lee, Hwa-Young Lee, Young-Je Lim, Ji-Hyun Kim, Su-Jin Jung, Eun-Soo Jung, Soo-Wan Chae, Juwon Lee, Junghyun Lim, Mohammad Mamun Ur Rashid, Kyung Hyun Min, and Han-Jung Chae from Jeonbuk National University and Jeonbuk National University Hospital supplemented 40 high fat diet (HFD) rats with 100–300 mg/kg/day of AGE to determine its efficacy in regulating vascular dysfunction. “[...] the primary aim of this study is to examine the inhibitory effects of AGE on dyslipidemia-associated vascular dysfunction, with a focus on its potential mechanisms of action.” The vascular relaxation responses to acetylcholine were impaired in HFD rats, while the administration of AGE restored the diminished relaxation pattern. Endothelial dysfunction, including increased plaque area, accumulated reactive oxygen species, and decreased nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) Ser1177 phosphorylation, were observed in HFD rats, whereas AGE reversed endothelial dysfunction and its associated biochemical signaling. Furthermore, AGE regulated endoplasmic reticulum (ER) stress and IRE1α sulfonation and its subsequent sirt1 RNA decay through controlling regulated IRE1α-dependent decay (RIDD) signaling, ultimately promoting NO bioavailability via the SIRT1-eNOS axis in aorta and endothelial cells. Independently, AGE enhanced AMPK phosphorylation, additionally stimulating SIRT1 and eNOS deacetylation and its associated NO bioavailability. Decursin, a prominent constituent of AGE, exhibited a similar effect in alleviating endothelial dysfunctions. These data suggest that AGE regulates dyslipidemia-associated vascular dysfunction by controlling ROS-associated ER stress responses, especially IRE1α-RIDD/sirt1 decay and the AMPK-SIRT1 axis. “Ultimately, this study presents clearly evidence that AGE is a promising natural product-based functional food/herbal medicine candidate for preventing or regulating hyperlipidemic cardiovascular complications.” DOI - https://doi.org/10.18632/aging.205343 Corresponding authors - Kyung Hyun Min - khmin1492@jbnu.ac.kr, and Han-Jung Chae - hjchae@jbnu.ac.kr About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Visit https://www.Aging-US.com and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ MEDIA@IMPACTJOURNALS.COM
In this episode, we're delving into the fascinating world of sirtuins, exploring their role in countering the 9 hallmarks of cellular aging, and uncovering ways to optimize their activity for our benefit. We'll be exploring 7 proven strategies, backed by scientific research, that can effectively boost the expression of these longevity-promoting sirtuins within the body. Topics: 1. Introduction - Overview of NAD+ and its role in energy metabolism - Previous discussion on strategies to increase NAD+ levels - Importance of NAD+ in other reactions such as those mediated by sirtuins 2. Sirtuins: Introduction and Background - Definition and origin of the term "sirtuins" - Discovery of sirtuins and their role in yeast aging - Transition from yeast cells to mammalian cells - Introduction to SIRT1 as a focus for exploration 3. SIRT1: NAD+-Dependent Histone Deacetylase - Role of SIRT1 as an NAD+-dependent histone deacetylase - Gene silencing / gene expression - SIRT1's influence on "genome stability" mediated by its ability to silence genes 4. SIRT1's Multi-Faceted Activities - Beyond histone deacetylation: SIRT1's reach to non-histone proteins - Deacetylation of p53 and suppression of cellular senescence - Enhancement of telomere integrity - Connecting these activities back to those 9 hallmarks of aging 5. The Sirtuin Enhancement Toolkit for Longevity: 7 Strategies - Resveratrol and Pterostilbene - Increasing NAD+ availability through various methods - Exercise's influence on SIRT1 expression - DHA (Omega-3 fatty acid) and its role in activating SIRT1 - Zinc's importance for SIRT1's structural integrity and function - Nutraceuticals: Berberine, quercetin, fisetin, and curcumin - Intermittent fasting and its impact on NAD+ levels and SIRT1 Thanks for tuning in! If you liked this episode, please leave a rating and review or share it to your stories over on Instagram. If you tag @synthesisofwellness, Chloe would love to personally thank you for listening! Follow Chloe on Instagram @synthesisofwellness Follow Chloe on TikTok @chloe_c_porter Visit synthesisofwellness.com to purchase products, subscribe to our mailing list, and more! Or visit linktr.ee/synthesisofwellness to see all of Chloe's links, schedule a BioPhotonic Scanner consult with Chloe, or support the show! Thanks again for tuning in! --- Support this podcast: https://podcasters.spotify.com/pod/show/chloe-porter6/support
Geoffrey Leung and Dr. Doris Leung, Senior Application Scientists from Insilico Medicine Hong Kong Ltd., detail a research paper they co-authored that was published by Aging (Aging-US) in Volume 15, Issue 8, entitled, "Identification of dual-purpose therapeutic targets implicated in aging and glioblastoma multiforme using PandaOmics - an AI-enabled biological target discovery platform.” #openaccess #aging #glioblastoma #research #ai #artificialintelligence #peerreview #openscience #researchpaper #journal #publication #meded #targetdiscovery #gbm DOI - https://doi.org/10.18632/aging.204678 Corresponding author - Mikhail Korzinkin - mike@insilicomedicine.com Abstract Glioblastoma Multiforme (GBM) is the most aggressive and most common primary malignant brain tumor. The age of GBM patients is considered as one of the disease's negative prognostic factors and the mean age of diagnosis is 62 years. A promising approach to preventing both GBM and aging is to identify new potential therapeutic targets that are associated with both conditions as concurrent drivers. In this work, we present a multi-angled approach of identifying targets, which takes into account not only the disease-related genes but also the ones important in aging. For this purpose, we developed three strategies of target identification using the results of correlation analysis augmented with survival data, differences in expression levels and previously published information of aging-related genes. Several studies have recently validated the robustness and applicability of AI-driven computational methods for target identification in both cancer and aging-related diseases. Therefore, we leveraged the AI predictive power of the PandaOmics TargetID engine in order to rank the resulting target hypotheses and prioritize the most promising therapeutic gene targets. We propose cyclic nucleotide gated channel subunit alpha 3 (CNGA3), glutamate dehydrogenase 1 (GLUD1) and sirtuin 1 (SIRT1) as potential novel dual-purpose therapeutic targets to treat aging and GBM. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204678 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, target discovery, GBM, glioblastoma, PandaOmics About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM
A new research paper was published in Aging (Aging-US) Volume 15, Issue 8, entitled, “Identification of dual-purpose therapeutic targets implicated in aging and glioblastoma multiforme using PandaOmics - an AI-enabled biological target discovery platform.” Glioblastoma Multiforme (GBM) is the most aggressive and most common primary malignant brain tumor. The age of GBM patients is considered as one of the disease's negative prognostic factors and the mean age of diagnosis is 62 years. A promising approach to preventing both GBM and aging is to identify new potential therapeutic targets that are associated with both conditions as concurrent drivers. In this new study, researchers Anastasia Shneyderman, Alexander Veviorskiy, Maria Dralkina, Simon Konnov, Olga Shcheglova, Frank W. Pun, Geoffrey Ho Duen Leung, Hoi Wing Leung, Ivan V. Ozerov, Alex Aliper, Mikhail Korzinkin, and Alex Zhavoronkov from The Youth Longevity Association, Pine Crest School Science Research Department, Shanghai High School International Division, and Insilico Medicine present a multi-angled approach of identifying targets, which takes into account not only the disease-related genes but also the ones important in aging. “For this purpose, we developed three strategies of target identification using the results of correlation analysis augmented with survival data, differences in expression levels and previously published information of aging-related genes.” Several studies have recently validated the robustness and applicability of AI-driven computational methods for target identification in both cancer and aging-related diseases. Therefore, the researchers leveraged the AI predictive power of the PandaOmics TargetID engine in order to rank the resulting target hypotheses and prioritize the most promising therapeutic gene targets. They propose three potentially novel dual-purpose therapeutic targets to treat aging and GBM: cyclic nucleotide gated channel subunit alpha 3 (CNGA3), glutamate dehydrogenase 1 (GLUD1) and sirtuin 1 (SIRT1). “The next steps towards implementation of the identified therapeutic targets into the clinic would involve a generation of small molecules and their optimisation with further validation and preclinical testing to determine their safety, efficacy, and potential side effects.” DOI: https://doi.org/10.18632/aging.204678 Corresponding author - Mikhail Korzinkin - mike@insilicomedicine.com Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204678 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, target discovery, GBM, glioblastoma, PandaOmics About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.29.534690v1?rss=1 Authors: Islam, A., Chen, X.-C., Weng, C.-W., Chen, C.-Y., Wang, C.-W., Chen, M.-K., Tikhomirov, A. S., Shchekotikhin, A. E., Chueh, P. J. Abstract: The antibiotic heliomycin (resistomycin), which is generated from Streptomyces resistomycificus, has multiple activities, including anticancer effects. Heliomycin was first described in the 1960s, but its clinical applications have been hindered by extremely low solubility. A series of 4-aminomethyl derivatives of heliomycin were synthesized to increase water solubility; studies showed that they had anti-proliferative effects, but the drug targets remained unknown. In this study, we conducted cellular thermal shift assays and molecular docking simulations to identify and validate the intracellular targets of heliomycin and its water-soluble derivative, 4-(dimethylaminomethyl)heliomycin (designated compound 4-dmH), in p53-functional SAS and p53-mutated HSC-3 oral cancer cells. Consistent with our in silico studies, our cellular thermal shift assays (CETSA) revealed that, in addition to SIRT1, the water-soluble 4-dmH preferentially targeted a tumor-associated NADH oxidase called tNOX or ENOX2. The direct binding of 4-dmH to tNOX inhibited the activity of tNOX and enhanced its ubiquitin-proteasomal protein degradation in both SAS and HSC-3 cells. Moreover, the inhibition of tNOX by 4-dmH decreased the oxidation of NADH to NAD+ which diminished NAD+-dependent SIRT1 deacetylase activity, ultimately inducing apoptosis and significant cytotoxicity in both cell types. We also observed that tNOX and SIRT1 were both upregulated in tumor tissues of oral cancer patients compared to adjacent normal tissues, suggesting their clinical relevance. Finally, the better therapeutic efficacy of 4-dmH was confirmed in tumor-bearing mice, which showed greater tNOX and SIRT1 downregulation and tumor volume reduction when treated with 4-dmH compared to heliomycin. Taken together, our in vitro and in vivo findings suggest that the multifaceted properties of water-soluble 4-dmH enable it to offer superior antitumor value compared to parental heliomycin, and indicated that it functions through targeting the tNOX-NAD+-SIRT1 axis to induce apoptosis in oral cancer cells. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Over the years, I've noticed that people veer away from supplements with complicated-sounding names like nicotinamide riboside (NR). That could be what's kept people in the dark so much about this specific form of vitamin B3. I have to admit that I ignored it for a while, when research papers began emerging several years ago, as well. But the health and fitness benefits are too good to ignore, which is why I decided it was time to write a guide covering what it is, how you might benefit from using it, how much to use, and a few other details about NR. You'll quickly see how it could be helpful for you or someone you know. What is Nicotinamide Riboside (NR)? Nicotinamide Riboside (NR) is a naturally occurring form of vitamin B3. As a precursor to nicotinamide adenine dinucleotide (NAD+), a critical coenzyme found in all living cells, NR maintains cellular energy and supports various biological processes.Canto, C., Menzies, K. J., & Auwerx, J. (2015). NAD+ metabolism and the control of energy homeostasis: a balancing act between mitochondria and the nucleus. Cell metabolism, 22(1), 31-53. https://doi.org/10.1016/j.cmet.2015.05.023 NAD+ is essential for cellular metabolism, DNA repair, and proper functioning of the mitochondria, the "powerhouses of the cell." As we age, our NAD+ levels naturally decline, contributing to various age-related health issues.Verdin, E. (2015). NAD+ in aging, metabolism, and neurodegeneration. Science, 350(6265), 1208-1213. https://doi.org/10.1126/science.aac4854 Research suggests that supplementation with NR may help boost NAD+ levels and combat these effects, improving overall health and well-being.Rajman, L., Chwalek, K., & Sinclair, D. A. (2018). Therapeutic potential of NAD-boosting molecules: the in vivo evidence. Cell metabolism, 27(3), 529-547. https://doi.org/10.1016/j.cmet.2018.02.011 You get trace levels of NR from dietary sources, such as milk, yeast, and some vegetables, but to consume NR at therapeutic levels, you need to supplement with it. Unlike other forms of vitamin B3, such as niacin and nicotinamide, NR maintains a better safety profile and produces fewer side effects.Conze, D., Brenner, C., & Kruger, C. L. (2019). Safety and metabolism of long-term administration of NIAGEN (nicotinamide riboside chloride) in a randomized, double-blind, placebo-controlled clinical trial of healthy overweight adults. Scientific Reports, 9(1), 9772. https://doi.org/10.1038/s41598-019-46120-z Fitness and Performance Benefits NR supplementation can improve muscle function, increase endurance, and enhance cellular energy production, making it a valuable supplement, especially for aging athletes. Improved Muscle Function One of the key benefits of NR supplementation is its positive impact on muscle function. An animal study found that NR supplementation increased muscle strength and improved exercise capacity. This is believed to result from NR's role in boosting nicotinamide adenine dinucleotide (NAD+), a crucial coenzyme involved in various cellular processes, including energy metabolism and mitochondrial function.Trammell SA, Schmidt MS, Weidemann BJ, et al. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun. 2016;7:12948. doi: 10.1038/ncomms12948 By enhancing NAD+ levels, NR supplementation may help promote muscle health and function, making it a valuable addition to any fitness regimen. Increased Endurance NR supplementation increases endurance performance, too. Another animal study demonstrated that supplementation with NR increased endurance due to the activation of sirtuin 1 (SIRT1), a protein critical in regulating energy metabolism and mitochondrial biogenesis.Cantó, C., Houtkooper, R. H., Pirinen, E., Youn, D. Y., Oosterveer, M. H., Cen, Y., ... & Sauve, A. A. (2012). The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metabolism, 15(6), 838-847.
“In this review, we focus on the decrease in nicotinamide adenine dinucleotide (NAD+) with age and the supplementation of NAD+ precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), in combination with other geroprotective compounds, to restore NAD+ levels present in youth.” #NAD #NMN #geroprotective Sharma A, Chabloz S, Lapides RA, Roider E, Ewald CY. Potential Synergistic Supplementation of NAD+ Promoting Compounds as a Strategy for Increasing Healthspan. Nutrients. 2023; 15(2):445. https://doi.org/10.3390/nu15020445 Aging, longevity, supplements, geroprotectors, SIRT1, NAD+, NMN, resveratrol, nutraceuticals, age-related diseases, flavonoids, senolytic, healthspan, EGCG, COQ10, Lycopene, Astaxanthin, Apigenein, luteolin, pterostilbene, betaine, quercetin, fisten, pronounce, CD38, PARP1, optimization, geroprotective Optimizing Longevity with NAD+ Boosters #NMN #NR #geroprotector #longevity #SIRT #CD38 #astaxanthin #lycopene #quercitin #EGCG #pterostilbene #PARP1 --- Support this podcast: https://podcasters.spotify.com/pod/show/ralph-turchiano/support
“In this review, we focus on the decrease in nicotinamide adenine dinucleotide (NAD+) with age and the supplementation of NAD+ precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), in combination with other geroprotective compounds, to restore NAD+ levels present in youth.” #NAD #NMN #geroprotective Sharma A, Chabloz S, Lapides RA, Roider E, Ewald CY. Potential Synergistic Supplementation of NAD+ Promoting Compounds as a Strategy for Increasing Healthspan. Nutrients. 2023; 15(2):445. https://doi.org/10.3390/nu15020445 Aging, longevity, supplements, geroprotectors, SIRT1, NAD+, NMN, resveratrol, nutraceuticals, age-related diseases, flavonoids, senolytic, healthspan, EGCG, COQ10, Lycopene, Astaxanthin, Apigenein, luteolin, pterostilbene, betaine, quercetin, fisten, pronounce, CD38, PARP1, optimization, geroprotective Optimizing Longevity with NAD+ Boosters #NMN #NR #geroprotector #longevity #SIRT #CD38 #astaxanthin #lycopene #quercitin #EGCG #pterostilbene #PARP1 --- Support this podcast: https://podcasters.spotify.com/pod/show/ralph-turchiano/support
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.24.523981v1?rss=1 Authors: O'Brien, J., Niehaus, P., Remark, J., Salimian, M., Kevas, Y., Rubin, S., Kristian, T., Chandrasekeran, K., Lu, C. P.-J., Russell, J., Ho, C.-Y. Abstract: Diabetic neuropathy (DN) is a debilitating disorder characterized by mechanical allodynia and sensory loss. It has traditionally been considered a small-fiber neuropathy, defined by the loss of free nerve endings in the epidermis. Free nerve endings, however, are nociceptors which may not be the only sensor for mechanical pain. To investigate the role of mechanoreceptors, specifically Meissner corpuscles, in the development of diabetic mechanical allodynia, our study focused on the keratinocyte-secreted brain-derived neurotrophic factor (BDNF) and its transcriptional regulator sirtuin 1 (SIRT1). Wild-type DN mice demonstrated decreased SIRT1 deacetylase activity, leading to a decrease in BDNF expression and Meissner corpuscle densities in foot skin. Epidermal SIRT1 knockout (KO) mice developed exacerbated DN phenotypes including severe mechanical allodynia, markedly reduced Meissner corpuscles, and subcutaneous A-beta axon degeneration. Among the major skin-derived neurotrophic factors, only BDNF was down-regulated in epidermal SIRT1 KO mice. With similar KO phenotypes, epidermal BDNF appeared to belong to the same pathway as SIRT1 in modulating diabetic mechanical allodynia. Furthermore, mice overexpressing epidermal SIRT1 showed BDNF up-regulation and improved DN phenotypes, supporting an important role of epidermal SIRT1 and BDNF in skin sensory apparatus regeneration and functional recovery in the setting of diabetes. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.09.523237v1?rss=1 Authors: Claude-Taupin, A., Roccio, F., Garfa-Traore, M., Regnier, A., Burtin, M., Morel, E., Terzi, F., Codogno, P., Dupont, N. Abstract: Shear stress generated by the urinary fluid flow is an important regulator of renal function. Its dysregulation is observed in various chronic and acute kidney diseases. Previously, we demonstrated that primary cilium-dependent autophagy allows kidney epithelial cells to adapt their metabolism in response to fluid flow. Here, we show that nuclear YAP/TAZ negatively regulates autophagy machinery in kidney epithelial cells subjected to fluid flow. This crosstalk is supported by a primary cilium-dependent activation of AMPK and SIRT1, independently of the Hippo pathway. We confirmed the relevance of the YAP/TAZ-autophagy molecular dialog in vivo using a zebrafish model of kidney development and a unilateral ureteral obstruction mouse model. In addition, an in vitro assay simulating the pathological flow observed at early stages of chronic kidney disease (CKD) activated YAP, leading to a primary cilium-dependent inhibition of autophagy. Our findings demonstrate the importance of YAP/TAZ and autophagy in the translation of fluid flow into cellular and physiological responses. Dysregulation of this pathway is associated with the early onset of CKD. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
A new research paper was published in Aging (listed as “Aging (Albany NY)” by MEDLINE/PubMed and “Aging-US” by Web of Science) Volume 14, Issue 20, entitled, “Age-associated changes in microglia activation and Sirtuin-1- chromatin binding patterns.” The aging process is associated with changes in mechanisms maintaining physiology, influenced by genetics and lifestyle, and impacting late life quality and longevity. Brain health is critical in healthy aging. Sirtuin 1 (Sirt1), a histone deacetylase with silencing properties, is one of the molecular determinants experimentally linked to health and longevity. In this new study, researchers Liana V. Basova, Nikki Bortell, Bruno Conti, Howard S. Fox, Richard Milner, and Maria Cecilia Garibaldi Marcondes from San Diego Biomedical Research Institute, University of Nebraska Medical Center and Oncovalent Therapeutics compared brain pathogenesis and Sirt1-chromatin binding dynamics in brain pre-frontal cortex from 2 groups of elder rhesus macaques (rhesus monkeys), divided by age of necropsy: shorter-lived animals (18-20 years old (yo)), equivalent to 60-70 human yo; and longer-lived animals (23-29 yo), corresponding to 80-100 human yo and modeling successful aging. These were compared with young adult brains (4-7 yo). “Our findings indicated drastic differences in the microglia marker Iba1, along with factors influencing Sirt1 levels and activity, such as CD38 (an enzyme limiting NAD that controls Sirt1 activity) and mir142 (a microRNA targeting Sirt1 transcription) between the elder groups.” Iba1 was lower in shorter-lived animals than in the other groups, while CD38 was higher in both aging groups compared to young. mir142 and Sirt1 levels were inversely correlated in longer-lived brains (>23yo), but not in shorter-lived brains (18-20 yo). They also found that Sirt1 binding showed signs of better efficiency in longer-lived animals compared to shorter-lived ones, in genes associated with nuclear activity and senescence. “Overall, differences in neuroinflammation and Sirt1 interactions with chromatin distinguished shorter- and longer-lived animals, suggesting the importance of preserving microglia and Sirt1 functional efficiency for longevity.” DOI: https://doi.org/10.18632/aging.204329 Corresponding Author: Maria Cecilia Garibaldi Marcondes - cmarcondes@SDBRI.org Keywords: aging, brain, rhesus macaques, microglia, Sirtuin-1 Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204329 Video: https://www.youtube.com/watch?v=Cz33TWM4so4 About Aging-US: Launched in 2009, Aging (Aging-US) publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at www.Aging-US.com and connect with us: SoundCloud – https://soundcloud.com/Aging-Us Facebook – https://www.facebook.com/AgingUS/ Twitter – https://twitter.com/AgingJrnl Instagram – https://www.instagram.com/agingjrnl/ YouTube – https://www.youtube.com/agingus LinkedIn – https://www.linkedin.com/company/aging/ Reddit – https://www.reddit.com/user/AgingUS Pinterest – https://www.pinterest.com/AgingUS/ For media inquiries, please contact media@impactjournals.com
This month on Episode 40 of Discover CircRes, host Cynthia St. Hilaire highlights four original research articles featured in the September 2 and September 16 issues of the journal. This episode also features an interview with Dr Jun Yoshioka, and Dr Yoshinobu Nakayama, from the City University of New York, about their study, Interaction of ARRDC-4 with GLUT1 Mediates Metabolic Stress in the Ischemic Heart. Article highlights: Jin, et al. Gut Dysbiosis Promotes Preeclampsia Mengozzi, et al. SIRT1 in Human Microvascular Dysfunction Hu, et al. Racial Differences in Metabolomic Profiles and CHD Garcia-Gonzales, et al. IRF7 Mediates Autoinflammation in Absence of ADAR1 Cindy St. Hilaire: Hi, and welcome to Discover CircRes, the podcast of the American Heart Association's journal, Circulation Research. I'm your host, Dr Cindy St. Hilaire from the Vascular Medicine Institute at the University of Pittsburgh. And today I'm going to be highlighting some articles from September 2nd, and September 16th issues of CircRes. And I'm also going to have a conversation with Dr Jun Yoshioka, and Dr Yoshinobu Nakayama, from the City University of New York, about their study, Interaction of ARRDC-4 with GLUT1 Mediates Metabolic Stress in the Ischemic Heart. But, before I get to the interview, I'm going to highlight a few articles. The first article is from our September 2nd issue, and it's titled, Gut Dysbiosis Promotes Preeclampsia by Regulating Macrophages, and Trophoblasts. The first author is Jiajia Jin, and the corresponding author is Qunye Zhang from the Chinese National Health Commission. Preeclampsia is a late-stage pregnancy complication that can be fatal to the mother, and the baby. It's characterized by high blood pressure, and protein in the urine. The cause is unknown, but evidence suggests the involvement of inflammation, and impaired placental blood supply. Because gut dysbiosis can influence blood pressure, and inflammation has been observed in preeclamptic patients, Jin and colleagues examined this link more closely. They found that women with preeclampsia had altered gut microbiome. Specifically, a reduction in a species of bacteria that produced short-chain fatty acids, and lower short-chain fatty acid levels in their feces, in their serum, and in their placentas. And preeclamptic women had lower short-chain fatty acid levels in their feces, in their serum, and in their placentas compared with women without preeclampsia. They found that fecal transfers from the preeclampsia women to rats with a form of the condition exacerbated the animals' preeclampsia symptoms, while fecal transfers from control humans alleviated the symptoms. Furthermore, giving rats an oral dose of short-chain fatty acids or short-chain fatty acid producing bacteria decreased the animals' blood pressure, reduced placental inflammation, and improved placental function. This work suggests that short-chain fatty acids, and gut microbiomes could be a diagnostic marker for preeclampsia. And microbial manipulations may even alleviate the condition. The second article I want to share is also from our September 2nd issue, and it's titled, Targeting SIRT1 Rescues Age and Obesity-Induced Microvascular Dysfunction in Ex Vivo Human Vessels. And this study was led by Alessandro Mengozzi from University of Pisa. With age, the endothelial lining of blood vessels can lose its ability to control vasodilation, causing the vessel to narrow and reduce blood flow. This decline in endothelial function has been associated with age related decrease in the levels of the enzyme, SIRT1. And artificially elevating SIRT1 in old mice improves animals' endothelial function. Obesity, which accelerates endothelial dysfunction, is also linked to low SIRT1 levels. In light of these SIRT1 findings, Mengozzi, and colleagues examined whether increasing the enzyme's activity could improve the function of human blood vessels. The team collected subcutaneous microvessels from 27 young, and 28 old donors. And both age groups included obese, and non-obese individuals. SIRT1 levels in the tissue were, as expected, negatively correlated with age and obesity, and positively correlated with baseline endothelium dependent vasodilatory function. Importantly, incubating tissue samples from older, and obese individuals with a SIRT1 agonist, restored the vessel's vasodilatory functions. This restoration involved a SIRT1 induced boost to mitochondrial function, suggesting that maintaining SIRT1 or its metabolic effect might be a strategy for preserving vascular health in aging, and in obesity. The third article I want to share is from our September 16th issue. And this one is titled, Differences in Metabolomic Profiles Between Black And White Women and Risk of Coronary Heart Disease. The first author is Jie Hu, and the corresponding author is Kathryn Rexrode, and they're from Brigham and Women's Hospital, and Harvard University. In the US, coronary heart disease, and coronary heart disease-related morbidity, and mortality is more prevalent among black women than white women. While racial differences in coronary heart disease risk factors, and socioeconomic status have been blamed, this group argues that these differences alone cannot fully explain the disparity. Metabolomic variation, independent of race, has been linked to coronary heart disease risk. Furthermore, because a person's metabolome is influenced by genetics, diet, lifestyle, environment and more, the authors say that it reflects accumulation of many cultural, and biological factors that may differ by race. This group posited that if racial metabolomic differences are found to exist, then they might partially account for differences in coronary heart disease risk. This study utilized plasma samples from nearly 2000 black women, and more than 4500 white women from several different cohorts. The team identified a racial difference metabolomic pattern, or RDMP, consisting of 52 metabolites that were significantly different between black, and white women. This RDMP was strongly linked to coronary heart disease risk, independent of race, and known coronary heart disease risk factors. Thus, in addition to socioeconomic factors, such as access to healthcare, this study shows that racial metabolomic differences may underlie the coronary heart disease risk disparity. The last article I want to share is also from our September 16th issue, and it is titled, ADAR1 Prevents Autoinflammatory Processes in The Heart Mediated by IRF7. The first author is Claudia Garcia-Gonzalez, and the corresponding author is Thomas Braun, and they are from Max Planck University. It's essential for a cell to distinguish their own RNA from the RNA of an invading virus to avoid triggering immune responses inappropriately. To that end, each cell makes modifications, and edits its own RNA to mark it as self. One type of edit made to certain RNAs is the conversion of adenosines to inosines. And this is carried out by adenosine deaminase acting on RNA1 or ADAR1 protein. Complete loss of this enzyme causes strong innate immune auto reactivity, and is lethal to mice before birth. Interestingly, the effects of ADAR1 loss in specific tissues is thought to vary. And the effect in heart cells in particular has not been examined. This study, which focused on the heart, discovered that mice lacking ADAR1 activity specifically in cardiomyocytes, exhibit autoinflammatory myocarditis that led to cardiomyopathy. However, the immune reaction was not as potent as in other cells lacking ADAR1. Cardiomyocytes did not exhibit the sort of upsurge in inflammatory cytokines, and apoptotic factors seen in other cells lacking ADAR1. And the animals themselves did not succumb to heart failure until 30 weeks of age. The author suggests that this milder reaction may ensure the heart resists apoptosis, and inflammatory damage because, unlike some other organs, it cannot readily replace cells. Cindy St. Hilaire: Today I have with me, Dr Jun Yoshioka, and Dr Yoshinobu Nakayama, and they're from City University of New York. And today we're going to talk about their paper, Interaction of ARRDC4 With GLUT1 Mediates Metabolic Stress in The Ischemic Heart. And this is in our September 2nd issue of Circulation Research. So, thank you both so much for joining me today. Jun Yoshioka: Thank you for having us. We are very excited to be here. Cindy St. Hilaire: It's a great publication, and also had some really great pictures in it. So, I'm really excited to discuss it. So, this paper really kind of focuses on ischemia, and the remodeling in the heart that happens after an ischemic event. And for anyone who's not familiar, ischemia is a condition where blood flow, and thus oxygen, is restricted to a particular part of the body. And in the heart, this restriction often occurs after myocardial infarctions, also called heart attacks. And so, cardiomyocytes, they require a lot of energy for contraction, and kind of their basic functions. And in response to this lack of oxygen, cardiomyocytes switch their energy production substrate. And so, I'm wondering if before we start talking about your paper, you can just talk about the metabolic switch that happens in a cardiac myocyte in the healthy state versus in the ischemic state. Jun Yoshioka: Sure. As you just said, that the heart never stops beating throughout the life. And it's one of the most energy demanding organs in the body. So, under normal conditions, cardiac ATP is mainly derived from fatty acid oxidation, and glucose metabolism contributes a little bit less in adult cardiomyocytes. However, under stress conditions such as ischemia, glucose uptake will become more critical when oxidative metabolism is interrupted by a lack of oxygen. That is because glycolysis is a primary anaerobic source of energy. We believe this metabolic adaptation is essential to preserve high energy phosphates and protect cardiomyocytes from lethal injuries. The concept of shifting the energy type of stress preference toward glucose, as you just said, has been actually long proposed as an effective therapy against MI. For example, GIK glucose insulin petition is classic. Now, let me explain how glucose uptake is regulated. Glucose uptake is facilitated by multiple isophones of glucose transporters in cardiomyocytes. Mainly group one and group four, and the minor, with a minor contribution of more recently characterized STLT1. In this study, we were particularly interested in group one because group one is a basal glucose transporter. Dr Ronglih Liao, and Dr Rong Tian's groups reported nearly two decades ago that the cardiac over-expression of group one prevents development of heart failure, and ischemic damage in mice. Since they are remarkable discoveries, the precise mechanism has not yet been investigated enough, at least to me. Especially how acute ischemic stress regulates group one function in cardiomyocytes. We felt that this mechanism is important because there is a potential to identify new strategies around group one, to reduce myocardiac ischemic damage. That is why we started this project hoping to review a new mechanism by which a protein family, called alpha-arrestins, controls cardiac metabolism under both normal, and diseased conditions. Cindy St. Hilaire: That is a perfect segue for my next question, actually, which is, you were focusing on this arrestin-fold protein, arrestin domain-containing protein four or ARRDC4. So, what is this family of proteins? What are arrestin-fold proteins? And before your study, what was known about a ARCCD4, and its relationship to metabolism, and I guess specifically cardiomyocyte metabolism? Jun Yoshioka: So, the arrestin mediated regulation of steroid signaling is actually common in cardiomyocytes. Especially beta, not the alpha, beta-arrestins have been well characterized as an adapter protein for beta-adrenergic receptors. Beta-arrestins combine to activate beta-adrenergic receptors on the plasma membrane, promote their endosomal recycling, and cause desensitization of beta-adrenergic signaling. Over the past decade, however, this family, the arrestin family, has been extended to include a new class of alpha-arrestins. But unlike beta-arrestins, the physiological functions of alpha-arrestins remain largely unclear based in mammalian cells. Humans, and mice have six members of alpha-arrestins including Txnip, thioredoxin interacting protein called Txnip, and five others named alpha domain-containing protein ARRDC1 2, 3, 4 and 5. Among them Txnip is the best studied alpha-arrestin. And Txnip is pretty much the only one shown to play a role in cardiac physiology. Txnip was initially thought to connect alternative stress and metabolism. However, it is now known that the Txnip serves as an adapter protein for the endocytosis of group one, and group four to mediate acute suppression of glucose influx to cells. In fact, our group has previously shown that the Txnip knockout mice have an enhanced glucose uptake into the peripheral tissues, as well as into the heart. Now, in this study, our leading player is ARRDC4. The arrestin-domains of ARRDC4 have 42% amino acid sequence similarities to Txnip. This means that the structurally speaking ARRDC4 is a brother to Txnip. So, usually the functions of arrestins are expected to be related to their conserved arrestin-domains. So, we were wondering whether two brothers, Txnip, and ARRDC4, may share the same ability to inhibit the glucose transport. That was a starting point where we initiated this project. Cindy St. Hilaire: That's great. And so, this link between ARRDC4, and the cardiac expression of gluten one and gluten four, I guess, mostly gluten one related to your paper, that really wasn't known. You went about this question kind of based on protein homology. Is that correct? Jun Yoshioka: That is right. Cindy St. Hilaire: And so, ARRDC4 can modulate glucose levels in the cell by binding, and if I understand it right, kind of helping that internalization process of glute one. Which makes sense. You know, when you have glucose come into the cell, you don't want too much. So, the kind of endogenous mechanism is to shut it off, and this ARRDC4 helps do that. But you also found that this adapter protein impacts cellular stress, and the cellular stress response. So, I was wondering if you could share a little bit more about that because I thought that was quite interesting. It's not just the metabolic impact of regulating glucose. There's also this cellular stress response. Jun Yoshioka: Right? So, Txnip is known to induce oxidative stress. But about the ARRDC4, we found that ARRDC4 actually does not induce oxidative stress. Instead, we found that it reproducibly causes ER, stress rather than oxidative stress. So, let Yoshinobu talk about the ER stress part. Yoshinobu, can you talk about how you found the ER stress story? Yoshinobu Nakayama: So, then let's talk about the, yeah, ER stress caused by ARRDC4. The ER stress caused by ARRDC4, year one was the biggest challenge in this study, because it's a little bit difficult to how we found a link of the glucose metabolism to the effect of the ARRDC4, only our stress. And at the other point of the project, we noticed that a ARRDC4 causes ER stress reproducibly, but we did not know how. So, both group one, and ARRDC4 are membrane proteins mainly localized near the plasma membrane. Then how does ARRDC4 regulate the biological process inside in the plasma radical? So, we then hypothesize that ARRDC4 induces intercellular glucose depravation by blocking cellular glucose uptake, and then interferes with protein glycosylation, thereby disturbing the ER apparatus. That makes sense because inhibition of group one trafficking by ARRDC4 was involved in the unfolded protein response in ischemic cardiomyocytes. Cindy St. Hilaire: So how difficult was that to figure out? How long did that take you? Yoshinobu Nakayama: How long? Yeah. Is this the question? Cindy St. Hilaire: It's always a hard question. Yoshinobu Nakayama: I think it's not several weeks. Maybe the monthly, months project. Yeah. Cindy St. Hilaire: Okay. It's always fun when, you know, you're focusing on one angle, and then all of a sudden you realize, oh, there's this whole other thing going on. So, I thought it was a really elegant tie-in between the metabolism, but also just the cellular stress levels. It was really nice. So, you created a full body knockout of ARRDC4 in the mouse, and you did all the proper kind of phenotyping. And at baseline everything's normal, except there's a little bit of changes in the blood glucose levels. But I also noticed when you looked at the expression of ARRDC4 in different tissues, it was very high in the lungs, and also in the intestines. And so, I know your study didn't focus on those tissues, but I was wondering if you could possibly speculate what ARRDC4 is doing in those tissues? Is it something similar? Do those cells under stress have any particular metabolic switching that's similar? Jun Yoshioka: Well, actually we don't have any complete answer for that question, because like you said, we didn't focus on lung, and other tissues. But I could say that actually the brother of ARRDC4, Txnip, is also highly expressed in lung, and bronchus, and in those organs. So, it's interesting because, which means that, the molecule is very oxygen sensitive, I will say. Both brothers. But that's all we know for now. But that's a very great point. And then we are excited to, you know. Cindy St. Hilaire. Yeah. Jun Yoshioka: Move on to the other tissues. Cindy St. Hilaire: I was thinking about it just because I've actually recently reviewed some papers on pulmonary hypertension. So, when I saw that expression, that was the first thing I thought of was, oh, they should put these mice in a sugen/hypoxia model, and see what happens. Jun Yoshioka: Right? Cindy St. Hilaire: So, there's an idea for you, Yoshinobu. A K-99 grant or something. And also, because it's a full body knockout, even when you're looking at the heart, obviously the cardiomyocytes are really the most metabolically active cell, but cardiac fibroblasts are also a major component of the heart tissue. And so, do you know, is the, I guess, effects or the protectiveness of the ARRDC4 knockout heart, is it mostly because of the role in the cardiomyocytes or is there a role for it also in the fibroblast? Yoshinobu Nakayama: Yeah, that's a very great question. Yeah. So, although we use the systemic knockout mice in the study, we believe that the beneficial effect of ARRDC4 deficiency is cardiac, autonomous. But this is because cardioprotection was demonstrated in the isolated heart experiments. But, you know, root is still uniformly expressing all cell types within the heart. To address this, we have tested the specific effects of ARRDC4 on cardiac fibroblasts, and inflammatory cells. ARRDC4 knockout hearts had a twofold increase in myocardial glucose uptake over wild-type hearts during insulin-free perfusion. However, an increase in glucose uptake in isolated cardiac fibroblast or inflammatory cells was relatively mild, with about 1.2 fold increase over wild-type cells. Thus we conclude that cardiomyocytes are the measure contributed to the cardiac metabolic shift. And then the mechanism within cardiomyocytes should play the major role in cardioprotection. Jun Yoshioka: I might, at one point, because, you know, the fibroblasts, they don't need to beat, right? Cindy St. Hilaire: Right. Jun Yoshioka: The inflammasome cells. They don't need to beat neither. So, they don't need that much energy. So, the cardiomyocytes energy metabolism is very important. So, that's why this mechanism is kind of more important in cardiomyocytes than other cell types. Cindy St. Hilaire: Yeah. And I think, you know, your phenotyping of the mice at baseline show that there's really no effect in a cell that's not under stress. So, it's really, really nice finding. Yeah. This article, I should say, is featured on the cover of the September 2nd Circulation Research issue. And it's got this really nice 3D modeling of the binding of ARRDC4 to glute one. And I was reading the paper, and the methods said, you use some AI for that. So, I'm sure other people have heard, too, AI in protein modeling is important. But AI in art, right? There's that new DALL-E 2 program. So how are you able to do this? How did that work? Jun Yoshioka: So, our study used is called AlphaFold, which applies the artificial intelligence-based deep learning method. AlphaFold, nowadays, everybody really is interested in AlphaFold. AlphaFold uses structural, and genetic data to come up with a model of what the protein of interest should look like. So, that is also how we got the protein structure, ARRDC4. We think that the ability of AlphaFold to precisely predict the protein structure from amino acid sequence would be a huge benefit to life sciences, including of course, cardiovascular science research, because of high cost, and technical difficulties in experimental methods. It's very useful if you can computationally predict the complex from individual structures of ARRDC4. And group one, which is actually structure of group one, is available in a protein data bank. But ARRDC4, it was not available. That's why we used AlphaFold. And then we use the docking algorithm called Hdoc. So, based on these AI analysis, we could successfully identify specific residues in a C terminal arrestin domain as an international interface, that regulates group one function. So, we believe this AI method will pretty much accelerate efforts to understand the protein, protein interactions. And we believe that will enable more advanced drug discovery, for example, in very near future. Cindy St. Hilaire: Yeah, it's really great. I started thinking about it in terms of some of the things I'm studying. So yeah, it was really nice. Jun Yoshioka: Try next time. Cindy St. Hilaire: Yeah, I will, I will. Actually, I went to the website, and was playing with it before I got on the call with you. So, how do you think your findings can be leveraged towards informing clinical decision making or even developing therapeutics? Jun Yoshioka: So, let me talk about what needs to be done. There are more things we must do. Cindy St. Hilaire: Always. Yeah. Jun Yoshioka: One of the most clinically relevant questions is whether ARRDC4 inhibition actually can mitigate development of post MI heart failure, and reduce mortality in the chronic phase, not the acute phase. Because in this paper we just did the seven day post MI, which is kind of like acute to subacute phase. But you never know what's going to happen in the chronic phase, right? And that is actually not so simple to answer because there are so many issues that you should consider. For example, Dr E. Dale Abel's lab has reported previously that cardiomyacites, specific group one, knockout in mice does not really accelerate the transition from compensated hypotrophy to heart failure. Also, the same group has shown that the overexpression group one does not actually prevent LV dysfunction in the mouse model of pressure overload. So, it is possible that ARRDC knockout can be, do much, or even harmful to LV remodeling in a chronic phase because chronic phase, it's not, it's getting hypoxy conditions, right? Cindy St. Hilaire: Yeah. So, it really might be something, I guess, personalized medicine is not the phrase I'm looking for. But I guess temporarily modulated, it would be something maybe we can figure out in an acute phase versus. Jun Yoshioka: Chronic phase. Cindy St. Hilaire: Yeah. Yeah. Jun Yoshioka: This makes sense. Because, you know, high capacity of ATP synthesis, by oxidating metabolism, could be important for chronic heart failure. So, it's selecting substrates. Energy substrates is no longer, you know, that issue. So, I'm not sure I'm answering your question, but this is the point that we consider to move on to the next. Cindy St. Hilaire: Well, that's great. And I think that was my next question, really. What is next? Are you really going to try to pinpoint where you could possibly target? Jun Yoshioka: Right. So, the first point we have to figure out about chronic phase, and another point we are interested in, is what's going on at the level of mitochondria. Does ARRDC4 knockout hearts have a different activity of electron transport chain or glycolytic enzymes within mitochondria? Cindy St. Hilaire: Or even mitochondrial fission infusion because it's, you know, it's a machinery. Jun Yoshioka: Yeah. And how about the other essential pathways in glucose metabolism such as mTOR, AMPK and HEF1, and so on. So, all these must be determined to help understand the more precise role of ARRDC4 in cardiac metabolism, we believe. Cindy St. Hilaire: It's a wonderful study, and now we have even more questions to ask using your great model. Congratulations again. Yoshinobu Nakayama: Thank you so much. Cindy St. Hilaire: Dr Yoshioka, and Dr Nakayama. Jun Yoshioka: Thank you. Cindy St. Hilaire: A wonderful paper, and congrats on getting the cover, and thank you so much for joining me today. Jun Yoshioka: Thanks well so much for having us. Yoshinobu Nakayama: Thank you. Cindy St. Hilaire: That's it for the highlights from our September 2nd, and our September 16th issues of Circulation Research. Thank you so much for listening. Please check out our CircRes Facebook page, and follow us on Twitter, and Instagram with the handle @circres, and hashtag discovercircres. Thank you to our guests, Dr Jun Yoshioka, and Dr Yoshinobu Nakayama. This podcast is produced by Ishara Ratnayaka, edited by Melissa Stonerm, and supported by the editorial team of Circulation Research. Some of the copy text for highlighted articles is provided by Ruth Williams. I'm your host, Dr Cindy St. Hilaire, and this is Discover CircRes, your on the go source for the most exciting discoveries in basic cardiovascular research. This program is copyright of the American Heart Association 2022. The opinions expressed by speakers in this podcast are their own, and not necessarily those of the editors or of the American Heart Association. For more information, please visit ahajournals.org.
Videos: 1. There was an unexpected 40% increase in 'all cause deaths' in 2021 (8:28) 2.Dr. Mike Yeadon: The Reason Why They Had to Use Genetic Vaccines 3. [PROOF] The Great Reset Is HAPPENING!- Russell Brand 4. Dr. Peter McCullough, MD, MPH, Jun 27, 2022 Texas Senate HHS Testimony 5. If I Were the Devil: Paul Harvey (Clean Audio Version) 6. A few highlights of a recent speech of mine that went slightly viral - Simon O'Connor (Simon David O'Connor MP is a New Zealand politician and a member of the New Zealand House of Representatives. He is a member of the National Party. He has represented the Tāmaki electorate since 2011. He is a member of the Foreign Affairs, Defence, and Trade committee). 7. Gun Control and The Vaule Of Life Health News: Cinnamon could stop Parkinson's in its tracks Leucine-rich protein supplements could benefit adults with sarcopenia Nutrients for the bones Searching for meaning? Try appreciating the small things Want a higher GPA in college? Join a gym Men's hot flashes: Hypnotic relaxation may ease the discomfort men don't talk about Cinnamon could stop Parkinson's in its tracks Rush University Medical Center, July 14, 2022 In an article appearing in the Journal of Neuroimmune Pharmacology indicates that cinnamon could one day be used by Parkinson's disease patients to prevent the disease from progressing. Saurabh Khasnavis and Kalipada Pahan, PhD, of Rush University Medical Center studied the effects of the spice in a mouse model of Parkinson's disease. They found that when cinnamon is metabolized into sodium benzoate in the blood and brain, the loss of beneficial proteins known as Parkin and DJ-1 is halted, while neurons that produce dopamine, a neurotransmitter that is reduced in Parkinson's, are protected. Motor function, which can be significantly impaired by the disease, was improved in animals that received cinnamon. "Cinnamon is metabolized in the liver to sodium benzoate, which is an FDA-approved drug used in the treatment for hepatic metabolic defects associated with hyperammonemia," explained lead researcher Dr Pahan "Cinnamon has been used widely as a spice throughout the world for centuries,” he noted. “This could potentially be one of the safest approaches to halt disease progression in Parkinson's patients." Leucine-rich protein supplements could benefit adults with sarcopenia Seoul National University College of Medicine, July 15 2022. Sarcopenia is a condition characterized by muscle wasting that contributes to frailty in aging men and women. Results from a meta-analysis of randomized trials reported in the Archives of Gerontology and Geriatrics concluded that protein supplements rich in the essential branched-chain amino acid leucine could improve muscle strength in sarcopenic individuals. “The treatment of choice for sarcopenia is still resistance exercise with nutritional supplementation because no pharmacological agents to treat sarcopenia have become available yet,” Sang Yoon Lee, MD, PhD, and colleagues at Seoul National University College of Medicine noted. The meta-analysis included 6 randomized, controlled trials that involved a total of 699 men and women with sarcopenia. Three hundred forty-six trial participants received a daily protein supplement containing 3 to 6 grams of leucine and 353 participants received a placebo or no leucine for 8 to 13 weeks. Muscle strength, muscle mass and physical performance were evaluated before and after the treatment periods. Muscle strength significantly improved in leucine-supplemented participants as a primary outcome in comparison with the control groups. There was also a trend toward improvement in muscle mass and physical performance in the groups that received leucine. There was no significant difference in response between lower and higher amounts of leucine. No serious adverse events were reported. Nutrients for the bones Catalytic Longevity Foundation, July 13 2022. A review appearing in the International Journal of Molecular Sciences describes how specific nutrients activate bone-preserving mechanisms. Osteoclasts are bone cells that break down bone tissue while osteoblasts synthesize bone. With respect to osteoblasts, the RUNX2 transcription factor is the master regulator of osteoblast formation and function, driving the transcription of a number of genes essential for the bone forming process. Signaling pathways that drive RUNX2 gene transcription are triggered by bone morphogenetic proteins (BMP) 2 and 4. AMPK, which is activated by G. pentaphyllum, hesperidin and metformin, promotes BMP 2 and 4 expression in osteoblasts. The protein Sirt1 promotes RUNX2 activity. Sirt1 activation is increased by melatonin, nicotinamide riboside, glucosamine and thymoquinone, found in Nigella sativa. Activation of soluble guanylate cyclase (sGC), the only known nitric oxide receptor, also leads to the promotion of RUNX2. High doses of biotin activate sGC. Nrf2 regulates the cells' defense against oxidative stress, as well as enhancing the activation of RUNX2 in osteoblasts and osteocytes. Lipoic acid, melatonin, thymoquinone, astaxanthin and sulforaphane can promote Nrf2 activity. Activation of these mechanisms also promotes autophagy, a process in which the cells consume their own damaged cellular components, which helps to prevent apoptosis (programmed cell death) and senescence in osteoblasts and osteocytes. “Regimens providing a selection of these nutraceuticals in clinically meaningful doses may have an important potential for preserving bone health,” the authors concluded. “Concurrent supplementation with taurine, N-acetylcysteine, vitamins D and K2, and minerals, including magnesium, zinc, and manganese, plus a diet naturally high in potassium, may also be helpful in this regard.” Searching for meaning? Try appreciating the small things Texas A&M University, July 18, 2022 Appreciating the intrinsic beauty in life's everyday moments can contribute to a more meaningful existence, according to new research. In a paper recently published in Nature Human Behavior, Joshua Hicks, a professor in the Texas A&M University Department of Psychological and Brain Sciences, says this may be a previously unaccounted for factor tied to perceptions of meaning. "It might not relate to whether you matter in the grand scheme of things, but we've shown people who value the little things, like your cup of coffee in the morning or being mindful in conversations with others, tend to have a high sense of meaning in life," he said. Hicks studies existential psychology. Put simply, he aims to understand the "big questions" in life. He describes his main focus as the experience of life—studying people's subjective feeling that their life has meaning. Scholars like Hicks generally agree there are three main sources of a subjectively meaningful existence: coherence, or the feeling that one's life "makes sense"; the possession of clear, long-term goals and sense of purpose; and existential mattering. This last factor, he says, is the belief that one's actions matter to others. What Hicks and his co-authors argue in their latest research is that appreciating and finding value in experiences, referred to as experiential appreciation, is a fourth fundamental pathway toward finding meaning in life. Want a higher GPA in college? Join a gym Michigan State University, July 10, 2022 For those students looking to bump up their grade point averages during college, the answer may not be spending more time in a library or study hall, but in a gym. New Michigan State University research shows that students who were members of the recreational sports and fitness centers on MSU's campus during their freshman and sophomore years had higher GPAs than those who weren't. The research also indicated that students with memberships stayed in school longer. An increase of 3.5 percent in two-year retention rates was seen among this group. The research supports previous theories suggesting that by creating an environment that connects students to an institution, in this case a university recreational facility, an increase in academic success and retention can occur. During the project, Pivarnik's team analyzed data from a sample of freshmen and sophomores, totaling 4,843 students, and compared the GPAs of those who purchased a fitness facility membership and those who did not. Results showed that after four consecutive semesters, the students with memberships obtained higher cumulative GPAs. They also had more credits completed by the end of their first year in college. Men's hot flashes: Hypnotic relaxation may ease the discomfort men don't talk about Baylor University, July 10, 2022 Men who experience hot flashes are unlikely to talk much about it, but they may find relief from their silent suffering if they are willing to try an unusual treatment, according to findings from a Baylor University case study. After seven weeks of hypnotic relaxation therapy, a 69-year-old man who had uncontrolled hot flashes following prostate cancer surgery showed a drastic decrease not only in hot flashes but also an impressive improvement in sleep quality, according to the study. Men's hot flashes are, of course, not related to estrogen, the primary female sex hormone. They occur in men with a history of prostate cancer — the second most common malignancy in men — or another disorder causing a testosterone deficiency. Up to 80 percent of prostate survivors experience hot flashes, and about 50 percent of those experience them as severe and needing treatment. What's more, hot flashes due to prostate cancer tend to be more frequent, more severe and more prolonged than those women experience. The new research follows previous published studies by Elkins that found a marked decrease in hot flashes among postmenopausal women and also among breast cancer survivors who have undergone hypnotic relaxation therapy. It reduced hot flashes by as much as 80 percent, and research findings by clinically trained therapists show it also improved participants' quality of life and lessened anxiety and depression. (Quality of life included such issues as work, sexuality, social and leisure activities, mood and concentration.)
Better Edge : A Northwestern Medicine podcast for physicians
Joseph Bass, MD, Ph.D. discusses the focus of his research on circadian rhythms and metabolic homeostasis. He tells us about the relationship between homeostasis and metabolism and the conclusions he has drawn from his recent study published in Nature Metabolism.He shares the significance of finding NADH inhibition of SIRT1 links energy state to transcription during time-restricted feeding and how he is incorporating these findings into his work at Northwestern Medicine.
ReferencesPrentice RL. Clinical trials and observational studies to assess the chronic disease benefits and risks of multivitamin-multimineral supplements.Am J Clin Nutr 2007, 85:308S-313S.NIH State-of-the-Science Conference Statement on Multivitamin/Mineral Supplements and Chronic Disease Prevention.NIH Consens State Sci Statements 2006, 23:1-30.Fortmann SP, Burda BU, Senger CA, et al. Vitamin and Mineral Supplements in the Primary Prevention of Cardiovascular Disease and Cancer: An Updated Systematic Evidence Review for the U.S. Preventive Services Task Force.Ann Intern Med 2013.Allen LH. How common is vitamin B-12 deficiency?Am J Clin Nutr 2009, 89:693S-696S.Hooshmand B, Solomon A, Kareholt I, et al. Homocysteine and holotranscobalamin and the risk of Alzheimer disease: a longitudinal study.Neurology 2010, 75:1408-1414.Morris MC, Evans DA, Tangney CC, et al. Dietary copper and high saturated and trans fat intakes associated with cognitive decline.Arch Neurol 2006, 63:1085-1088.de Bortoli MC, Cozzolino SM. Zinc and selenium nutritional status in vegetarians.Biol Trace Elem Res 2009, 127:228-233.Burnett-Hartman AN, Fitzpatrick AL, Gao K, et al. Supplement use contributes to meeting recommended dietary intakes for calcium, magnesium, and vitamin C in four ethnicities of middle-aged and older Americans: the Multi-Ethnic Study of Atherosclerosis.J Am Diet Assoc 2009, 109:422-429.Yang Q, Cogswell ME, Hamner HC, et al. Folic acid source, usual intake, and folate and vitamin B-12 status in US adults: National Health and Nutrition Examination Survey (NHANES) 2003-2006.Am J Clin Nutr 2010, 91:64-72.Troesch B, Hoeft B, McBurney M, et al. Dietary surveys indicate vitamin intakes below recommendations are common in representative Western countries.Br J Nutr 2012, 108:692-698.Bitterman KJ, Anderson RM, Cohen HY, et al. Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1.J Biol Chem 2002, 277:45099-45107.Baggott JE, Oster RA, Tamura T. Meta-analysis of cancer risk in folic acid supplementation trials.Cancer Epidemiol 2011.Stranges S, Navas-Acien A, Rayman MP, Guallar E. Selenium status and cardiometabolic health: state of the evidence.Nutrition, metabolism, and cardiovascular diseases : NMCD 2010, 20:754-760.
Aging-US published a Special Collection on Eye Disease which included "Loss of NAMPT in aging retinal pigment epithelium reduces NAD+ availability and promotes cellular senescence" which reported that retinal pigment epithelium performs numerous functions critical to retinal health and visual function. Here, the authors evaluated the temporal expression of key nicotinamide adenine dinucleotide -biosynthetic genes and associated levels of NAD+, a principal regulator of energy metabolism and cellular fate, in mouse RPE. They simulated in vitro the age-dependent decline in NAD+ and the related increase in RPE senescence in human and mouse primary RPE using the NAMPT inhibitor FK866 and demonstrated the positive impact of NAD+-enhancing therapies on RPE cell viability. This was confirmed in vivo in the RPE of mice injected sub-retinally with FK866 in the presence or absence of nicotinamide mononucleotide. Dr. Pamela M. Martin and Dr. Ravirajsinh N. Jadeja said, "The retinal pigment epithelium (RPE) performs numerous functions essential to normal retinal health and function." RPE serves as a physiologic barrier between the photoreceptor cells and the choroidal blood supply and in doing so, plays an essential role in protecting the retina from systemic insults by regulating immune responses and thereby limiting the entry of infectious or otherwise detrimental agents into retina. This is the premise of a number of recent studies including the present investigation in which we focused on nicotinamide adenine dinucleotide and factors governing its bioavailability in relation to the overall impact on RPE viability. NAD+, a central metabolic cofactor, plays a critical role in regulating cellular metabolism and energy homeostasis. The ratio of NAD+ to NADH regulates the activity of various enzymes essential to metabolic pathways including glycolysis, the Kreb's cycle, and fatty acid oxidation. There is a wealth of clinical and experimental data stemming from studies of other primary diseases of aging demonstrating clearly a generalized decline in the availability of NAD+ in association with increased age and the related reduction in the activity of a number of downstream metabolic pathways that contribute to the development and progression of degenerative processes. Members of the sirtuin family, poly ADP-ribose polymerases and the efficacy of therapies capable of impacting them have been evaluated in the context of aging retina and RPE. However, little attention has been given to upstream factors that regulate NAD+ biosynthesis, particularly in RPE. Given the importance of RPE to retinal health and function, in the present investigation we focused on evaluating the impact of NAD+ and factors that regulate its availability on RPE viability both in vivo and in vitro. This finding is highly relevant to the clinical management of AMD but perhaps also broadly to the management of other degenerative retinal diseases in which RPE is prominently affected. The Martin/Jadeja Research Team concluded in their Aging-US Research Output that these present data demonstrating an age-dependent decline in NAMPT expression and in turn, NAD+ generation in RPE which ultimately promotes RPE senescence supports strongly the rationale for enhancing NAMPT expression and associated NAD+ generation therapeutically. Based upon the present experimental observations, future preclinical studies evaluating NMN or other therapies that have a direct impact on NAMPT expression and NAD+ metabolism in the context of aging and age-related retinal disease development and progression are highly warranted. Full Text - https://www.aging-us.com/article/101469/text Correspondence to: Pamela M. Martin email: pmmartin@augusta.edu and Ravirajsinh N. Jadeja email: rjadeja@augusta.edu Keywords: retinal pigment epithelium (RPE), aging, age-related macular degeneration, NAD+, NAMPT, senescence, SIRT1
Treatment with Rhodiola mimics exercise to resist high-fat diet-induced muscle dysfunction Central South University (China), April 30, 2021 According to news reporting out of Changsha, People’s Republic of China, research stated, “Muscle dysfunction is a complication of high-fat diet (HFD)-induced obesity that could be prevented by exercise, but patients did not get enough therapeutic efficacy from exercise due to multiple reasons.” The news reporters obtained a quote from the research from Xiangya Hospital of Central South University: “To explore alternative or supplementary approaches to prevent or treat muscle dysfunction in individuals with obesity, we investigated the effects of Rhodiola on muscle dysfunction as exercise pills. SIRT1 might suppress atrogenes expression and improve mitochondrial quality control, which could be a therapeutic target stimulated by exercise and Rhodiola, but further mechanisms remain unclear. We verified the lipid metabolism disorders and skeletal muscle dysfunction in HFD feeding mice. Moreover, exercise and Rhodiola were used to intervene mice with a HFD. Our results showed that exercise and Rhodiola prevented muscle atrophy and dysfunction in obese mice and activating the SIRT1 pathway, while atrogenes were suppressed and mitochondrial quality control was improved. EX-527, SIRT1 inhibitor, was used to validate the essential role of SIRT1 in salidroside benefit.” According to the news editors, the research concluded: “Results of cell culture experiment showed that salidroside alleviated high palmitate-induced atrophy and mitochondrial quality control impairments, but these improvements of salidroside were inhibited by EX-527 in C2C12 myotubes. Overall, Rhodiola mimics exercise that activates SIRT1 signaling leading to improvement of HFD-induced muscle dysfunction.” Prenatal exposure to pesticides increases the risk of obesity in adolescence First study to analyse the long-term effects of persistent organic pollutants on cardiometabolic risk in adolescents Barcelona Institute for Global Health (Spain), May 3, 2021 Exposure before birth to persistent organic pollutants (POPs)-- organochlorine pesticides, industrial chemicals, etc.--may increase the risk in adolescence of metabolic disorders, such as obesity and high blood pressure. This was the main conclusion of a study by the Barcelona Institute for Global Health (ISGlobal), a research centre supported by the "la Caixa" Foundation. The study was based on data from nearly 400 children living in Menorca, who were followed from before birth until they reached 18 years of age. POPs are toxic, degradation-resistant chemicals that persist in the environment. Examples of such compounds are pesticides and organochlorine insecticides (DDT, etc.). POPs have adverse effects on both human health and the environment and their use is regulated globally. Prenatal exposure to these substances has been associated with cardiometabolic risk factors in childhood, but there were previously no studies assessing whether such associations continue into adolescence, a developmental stage characterised by significant changes in the endocrine system and rapid increases in body mass. The aim of this investigation, carried out within the framework of the INMA Project-Environment and Childhood, was to study the associations between prenatal exposure to POPs and body mass index (BMI) as well as other markers of cardiovascular risk in adolescence. Data from 379 children in Menorca was analysed. POP levels were measured in umbilical cord blood samples and the children were then seen periodically between the ages of 4 and 18 years. At these visits, BMI, body fat percentage and blood pressure were recorded as they grew. When the child reached 14 years of age, the scientists measured blood biomarkers of cardiometabolic risk (cholesterol, triglycerides, glucose, etc.). The results of this study, published in the journal Environment International, suggest an association between prenatal POP exposure and a higher BMI in adolescence, particularly in the case of the fungicide hexachlorobenzene (HCB) and the insecticide compound dichloro-diphenyl-trichloroethane (DDT). Exposure to these two organochlorides--HCB and DDT¬--was also associated with higher blood pressure in childhood and adolescence and increased cardiometabolic risk at 14 years of age. ISGlobal researcher Núria Güil-Oumrait, the first author of the study, explains that "this is the first longitudinal study to analyse the relationship between persistent organic pollutants and cardiometabolic risk throughout childhood and adolescence. Our findings show that the association between these substances and infant BMI does persist into adolescence and that prenatal exposures are associated with the main risk factors for metabolic syndrome in adults, a condition that today affects one in four people worldwide. With respect to the mechanisms that might explain this association, Güil-Oumrait points out that "it is thought that POPs may interact with hormone receptors or with the generation of free radicals, and the chief problem is that these pollutants accumulate in the fatty tissues of living organisms, where they can persist for years, even decades". Martine Vrijheid, study coordinator and head of the Childhood and Environment Programme at ISGlobal, highlights the fact that "some of these substances could be considered endocrine disruptors, that is, chemicals that interfere with hormonal regulation". In her view "more studies are needed in this field, especially focussing on childhood and adolescence, which are critical developmental stages characterised by particular vulnerability". One cup of leafy green vegetables a day lowers risk of heart disease Research has found that by eating just one cup of nitrate-rich vegetables each day people can significantly reduce their risk of heart disease. Edith Cowan University (Australia), May 4, 2021 New Edith Cowan University (ECU) research has found that by eating just one cup of nitrate-rich vegetables each day people can significantly reduce their risk of heart disease. The study investigated whether people who regularly ate higher quantities of nitrate-rich vegetables, such as leafy greens and beetroot, had lower blood pressure, and it also examined whether these same people were less likely to be diagnosed with heart disease many years later. Cardiovascular diseases are the number one cause of death globally, taking around 17.9 million lives each year. Researchers examined data from over 50,000 people residing in Denmark taking part in the Danish Diet, Cancer, and Health Study over a 23-year period. They found that people who consumed the most nitrate-rich vegetables had about a 2.5 mmHg lower systolic blood pressure and between 12 to 26 percent lower risk of heart disease. Lead researcher Dr Catherine Bondonno from ECU's Institute for Nutrition Research said identifying diets to prevent heart disease was a priority. "Our results have shown that by simply eating one cup of raw (or half a cup of cooked) nitrate-rich vegetables each day, people may be able to significantly reduce their risk of cardiovascular disease," Dr Bondonno said. "The greatest reduction in risk was for peripheral artery disease (26 percent), a type of heart disease characterised by the narrowing of blood vessels of the legs, however we also found people had a lower risk of heart attacks, strokes and heart failure." Forget the supplements The study found that the optimum amount of nitrate-rich vegetables was one cup a day and eating more than that didn't seem to give any additional benefits. "People don't need to be taking supplements to boost their nitrate levels because the study showed that one cup of leafy green vegetables each day is enough to reap the benefits for heart disease," Dr Bondonno said. "We did not see further benefits in people who ate higher levels of nitrate rich vegetables." Smoothies are ok Dr Bondonno said hacks such as including a cup of spinach in a banana or berry smoothie might be an easy way to top up our daily leafy greens. "Blending leafy greens is fine, but don't juice them. Juicing vegetables removes the pulp and fibre," Dr Bondonno said. The paper "Vegetable nitrate intake, blood pressure and incident cardiovascular disease: Danish Diet, Cancer, and Health Study" is published in the European Journal of Epidemiology. It is a collaboration between Edith Cowan University, the Danish Cancer Society and The University of Western Australia. The research adds to growing evidence linking vegetables generally and leafy greens specifically with improved cardiovascular health and muscle strength. This evidence includes two recent ECU studies exploring cruciferous vegetables and blood vessel health and green leafy vegetables and muscle strength. Mindfulness programs can boost children's mental health University of Derby (UK), May 4, 2021 Mindfulness programs can improve the mental health of school-age children and help them to feel more optimistic, according to new research from the University of Derby and Derbyshire Educational Psychology Service. More than 1,000 pupils aged between 9-12 years old across 25 schools in Derbyshire, received one 45-minute mindfulness session per week for nine weeks during the year-long project, which involved a collaboration between Dr. William Van Gordon, Associate Professor in Contemplative Psychology at the University, and Derbyshire Educational Psychology Service. Mindfulness is an ancient meditation technique that involves focussing awareness on the present moment, as a means of fostering calm, wellbeing and insight. The weekly sessions involved activities such as practicing mindful breathing and paying attention to bodily sensations, as well as exercises intended to help cultivate attention skills and a greater awareness of emotions. The impact of the sessions, which were delivered by teachers in a traditional classroom environment, was evaluated by comparing psychological assessments that the children completed before the classes began, with assessments undertaken after the program had concluded. Part of the evaluation measured children's emotional resiliency using The Resiliency Scale for Children, while wellbeing was rated using the Stirling Children's Wellbeing Scale. Overall, the study found a significant improvement in positive emotional state, outlook and resiliency. There was also an increase in the different dimensions of resilience: optimism increased by 10%, tolerance was improved by 8% and self-efficacy, how a child feels they can cope with a situation based on the skills they have and the circumstances they face, improved by 11%. Professor Van Gordon said: "Findings from the study indicate that mindfulness delivered by school teachers can improve wellbeing and resiliency in children and young people. "This is consistent with wider evidence demonstrating the positive impact of mindfulness on school children's levels of emotional resiliency, emotional stability, wellbeing and stress. "These findings are also in line with the view that preventative interventions given at a young age can help to reduce the incidence of mental health problems in young people." Vitamin D levels higher in exercisers Johns Hopkins University, May 01 2021 The issue of the Journal of Clinical Endocrinology & Metabolism published the finding of researchers at Johns Hopkins University of a correlation between increased physical activity and higher levels of vitamin D. Higher levels of vitamin D and exercise was also associated with a lower risk of cardiovascular disease. The study included 10,342 men and women who were free of coronary heart disease and heart failure upon enrollment in the Atherosclerosis Risk in Communities study. Physical activity levels were assessed during follow-up visits that took place over a 19.3-year period. Stored serum samples obtained at the second visit were analyzed for 25-hydroxyvitamin D3. Subjects who achieved American Heart Association recommended physical activity levels had average levels of vitamin D that were higher than those who had intermediate and poor levels of activity. Following adjustment for lifestyle and other factors, those who met the recommended levels had a 31% lower risk of being deficient in vitamin D than those with poor activity levels. Subjects in the recommended activity group with levels of vitamin D of 30 ng/mL or more had a 24% lower risk of cardiovascular disease. The association between exercise and vitamin D was stronger in subjects of European ethnicity than among African Americans. The authors noted that European-Americans as well as those who engage in exercise are likelier to be supplement users. “We did find that vitamin D supplement use was higher among those with increased physical activity,” they observed. "In our study, both failure to meet the recommended physical activity levels and having vitamin D deficiency were very common" stated coauthor Erin Michos, MD, MS, of Johns Hopkins University School of Medicine. "The bottom line is we need to encourage people to move more in the name of heart health." One teaspoon daily of trehalose can help maintain glucose homeostasis: a double-blind, randomized controlled trial Hayashibara Co. Ltd (Japan), April 24, 2021 Background Trehalose is a natural disaccharide that is widely distributed. A previous study has shown that daily consumption of 10 g of trehalose improves glucose tolerance in individuals with signs of metabolic syndrome. In the present study, we determined whether a lower dose (3.3 g/day) of trehalose improves glucose tolerance in healthy Japanese volunteers. Methods This was a randomized, double-blind, placebo-controlled study of healthy Japanese participants (n = 50). Each consumed 3.3 g of trehalose (n = 25) or sucrose (n = 25) daily for 78 days. Their body compositions were assessed following 0, 4, 8, and 12 weeks; and serum biochemical parameters were assayed and oral 75-g glucose tolerance tests were performed at baseline and after 12 weeks. Results There were similar changes in body composition and serum biochemistry consistent with established seasonal variations in both groups, but there were no differences in any of these parameters between the two groups. However, whereas after 12 weeks of sucrose consumption, the plasma glucose concentration 2 h after a 75-g glucose load was significantly higher than the fasting concentration, after 12 weeks of trehalose consumption the fasting and 2-h plasma glucose concentrations were similar. Furthermore, an analysis of the participants with relatively high postprandial blood glucose showed that the plasma glucose concentration 2 h after a 75-g glucose load was significantly lower in the trehalose group than in the sucrose group. Conclusions Our findings suggest that trehalose helps lower postprandial blood glucose in healthy humans with higher postprandial glucose levels within the normal range, and may therefore contribute to the prevention of pathologies that are predisposed to by postprandial hyperglycemia,, even if the daily intake of trehalose is only 3.3 g, an amount that is easily incorporated into a meal. Coffee compound enhances autophagy to protect against cell injury Chengdu University of Traditional Chinese Medicine (China), April 30, 2021 According to news reporting originating from Sichuan, People’s Republic of China, research stated, “Autophagy serves an important role in amyloid-beta (A beta) metabolism and tau processing and clearance in Alzheimer’s disease. The progression of A beta plaque accumulation and hyperphosphorylation of tau proteins are enhanced by oxidative stress.” Our news editors obtained a quote from the research from the Chengdu University of Traditional Chinese Medicine, “A hydrogen peroxide (H2O2) injury cell model was established using SH-SY5Y cells. Cells were randomly divided into normal, H2O2 and chlorogenic acid (5-caffeoylquinic acid; CGA) groups. The influence of CGA on cell viability was evaluated using a Cell Counting Kit-8 assay and cell death was assessed using Hoechst 33342 nuclear staining. Autophagy induction and fusion of autophagic vacuoles assays were performed using monodansylcadaverine staining. Additionally, SH-SY5Y cells expressing Ad-mCherry-green fluorescent protein-LC3B were established to detect autophagic flow. LysoTracker Red staining was used to evaluate lysosome function and LysoSensor ™ Green staining assays were used to assess lysosomal acidification. The results demonstrated that CGA decreased the apoptosis rate, increased cell viability and improved cell morphology in H2O2-treated SH-SY5Y cells. Furthermore, CGA alleviated the accumulation of autophagic vacuoles, reduced the LC3BII/I ratio and decreased P62 levels, resulting in increased autophagic flux. Additionally, CGA upregulated lysosome acidity and increased the expression levels of cathepsin D. Importantly, these effects of CGA on H2O2-treated SH-SY5Y cells were mediated via the mTOR-transcription factor EB signaling pathway.” According to the news editors, the research concluded: “These results indicated that CGA protected cells against H2O2-induced oxidative damage via the upregulation of autophagosomes, which promoted autophagocytic degradation and increased autophagic flux.” This research has been peer-reviewed.
Doctor Purser talks about his: TOP 10+ APOE4 TIPS FOR KEEPING IT AT BAY!!! 1. First of all APOE errors are toxic and cause dementia (Alzheimer’s Disease).If you have APOE4 errors then you have a 50% chance of having Alzheimer’s Disease. 2. The APOE4 error causes more than half of all LOAD (Late Onset Alzheimers Disease) cases. “The APOE4 gene is the strongest and only confirmed genetic risk factor for the development of late onset Alzheimer’s disease (LOAD), which enhances the risk level by three times in heterozygous individuals, and twelve times increased risk in homozygous patients.” 3. APOE4 dementia prevention is about preventing brain inflammation. Inflammation causes fibrillary plaque build up or aggregation. 4. Reduced Glutathione prevents cholesterol conversion into plaque. 550mg per day. Must be validatable, absorbable, reduced. If someone would only make one of these... 5. Fish oil, specifically the DHA portion of fish oil, and more specifically, it has to be the PHOSPHOLIPID form of fish oil (only version that passes the BLOOD BRAIN BARRIER), will do this. So it must be krill oil, mainly astaxanthin krill oil that has a content of greater than 2mg of astaxanthin and is more then 35% PHOSPHOLIPID DHA with an overall dose of the PHOSPHOLIPID DHA being at least 600mg per day with 2 mg of it being ASTAXANTHIN KRILL OIL. Got it? (THERE ARE ONLY TWO ON THE MARKET THAT DOSE THIS AND ONE IS A LOT BETTER THAN THE OTHER.) 6. RESVERATROL, in the purified TRANS-RESVERATROL form, at 200mg per day, prevents the inflammation and reduces the risk of dementia from APOE4 by acting as the ultimate SIRT1 activator which protects your brain from plaque formation and inflammation. It does about two dozen good things for your brain. 7. QUERCITIN at 500mg a day 8. LITHIUM OROTATE 2.5mg/day. Not the drug but the supplement. 9. VITAMIN C — 500mg a day. VITAMIN C AND E IN MEN WITH APOE4. 10. EXERCISE 1-4-7 (1 hour of walking per day, 4mph — i.e. a brisk walk, and 7 days per week). 11. AVOID SWEETS AND SUGAR. 12. STATINS — simvastatin use definitely helped prevent cognitive decline especially in APOE4 cases. 13. METFORMIN— small dose has been shown to reduce occurrence of Alzheimers in APOE4 cases. 14. CONTROL YOUR FIBROMYALGIA — runaway severe fibro means a LOT of inflammation in the brain. Deal with it appropriately. Copper and zinc dysmetabolism seems to be impactful on APOE4 Alzheimer’s disease risk. Eat a low copper diet! 15. VALIDATED AND NATURAL BIOPQ+MICROUBIQUINOL — 2/DAY. UP TO 30% IMPROVEMENT IN MEMORY AFTER 6 WEEKS. For original facebook post: https://business.facebook.com/danpursermd/videos/796334737650156/
In this podcast Fred Herbert shares scientific research that is extremely promising for reversing age related damage to our blood vessels. Cardio Vascular Disease is the number one cause of death globally and preventing it will have a huge impact on our longevity. The focus of this podcast is NMN (Nicotinamide Mononucleotide) and the research on mice that showed it could restore the arteries of old mice to look young again and improved their exercise performance.
TAME (Targeting Aging with Metformin) aims to slow the aging process. It has been developed and approved by the National Institute of Aging and the FDA. The principal investigator, Nir Barzilai, is excited about changing the paradigm and getting big PHARMA to actually fund research for drugs (like metformin) for anti-aging. Getting older is associated with heart disease, kidney disease, cancer, dementia, among other things. This is where metformin comes in. It helps slow down the major biochemical challenge of aging: glucose metabolism. Enzymes like insulin membrane receptors, mTOR, AMPK, and SIRT1 are implicated. And they are positively impacted by metformin. Metformin is cheap (free at many pharmacies now). It's been used for decades. It's popular (the #1 oral drug for early type 2 diabetes). And it's safer than you think. Some medical sites (like Mayo) still incorrectly list lactic acidosis as a problem with metformin. But look up the multiple Cochrane analyses on this. For more information, contact us at 859-721-1414 or myhealth@prevmedheartrisk.com. Also, check out the following resources: PrevMed's article on metforminPrevMed's websitePrevMed's YouTube channelPrevMed's Facebook page
Mitochondria are the powerhouses of the cell. They are critical to health and longevity. As we age, DNA processes begin to fail. These failures can come from damage to DNA or from decreased transcription of genes. These genes make proteins (enzymes) that are critical to cellular respiration, or the process of getting energy out of food. Some of these enzyme names are becoming familiar - AMPK, SIRT1 and the SIRTUINS, p53, and ATM. Dr. Sreekumaran Nair at Mayo Clinic in Rochester, New York, did a unique study and published his results in March 2017. He had two groups involved; 1 group age 18-30, and another group 65-80. Both groups did HIIT (High Intensity Interval Training) for 3 months. Cardiovascular and lung function improved 28% in the younger group and 17% in the older group. Here's the unusual part. Muscle biopsies were done, showing actual metabolic, cellular changes in mitochondrial function. The older group had a 69% improvement in mitochondrial function. The younger group had a 49% improvement. One review of this study stated that HIIT doesn't really make you younger. It went on to say that eating too many doughnuts could overweigh the positive impacts of the HIIT. That seems obvious to me. I think we want to have mitochondria that perform on a healthy level. That is, if we want to be healthy.For more information, contact us at 859-721-1414 or myhealth@prevmedheartrisk.com. Also, check out the following resources: PrevMed's blogPrevMed's websitePrevMed's YouTube channelPrevMed's Facebook page
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.08.371922v1?rss=1 Authors: Alquezar, C., Schoch, K. M., Geier, E. G., Ramos, E. M., Scrivo, A., Li, K., Argouarch, A. R., Mlynarski, E. E., Dombroski, B., Yokoyama, J. S., Cuervo, A. M., Burlingame, A. L., Schellenberg, G. D., Miller, T. M., Miller, B. L., Kao, A. W. Abstract: Age-associated neurodegenerative disorders demonstrating tau-laden intracellular inclusions, including Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) and progressive supranuclear palsy (PSP), are collectively known as tauopathies. The vast majority of human tauopathies accumulate non-mutant tau rather than mutant forms of the protein, yet cell and animal models for non-mutant tauopathies are lacking. We previously linked a monoallelic mutation in the TSC1 gene to tau accumulation and FTLD. Now, we have identified new variants in TSC1 that predisposed to other tauopathies such as AD and PSP. These new TSC1 risk variants significantly decreased the half-life of TSC1/hamartin in vitro. Cellular and murine models of TSC1 haploinsufficiency (TSC1+/-) accumulated tau protein that exhibited aberrant acetylation on six lysine residues. Tau acetylation hindered its degradation via chaperone-mediated autophagy leading to neuronal tau accumulation. Enhanced tau acetylation in TSC1+/- models was achieved through both an increase in p300 acetyltransferase activity and a decrease in SIRT1 deacetylase levels. Pharmacological modulation of either enzyme restored tau levels. Together, these studies substantiate TSC1 as a novel tauopathy risk gene and advance TSC1 haploinsufficiency as a new genetic model for tauopathy. In addition, these results promote acetylated tau as a rational target for diagnostic and therapeutic modalities in multiple tauopathies. Copy rights belong to original authors. Visit the link for more info
The pineal endocrine hormone melatonin proximally decreasesIL-1β-induced MMP production by inhibiting Sirt1-dependent NAMPT and NFAT5 signaling in chondrocytes; since autoinflammatory Osteoarthritis (OA) is a degenerative joint (cartilage degradation) disease linked to human aging and Interleukin-1β contributes to OA pathogenesis by enhancing oxidative stress and inflammation the role(s) of sirtuin and NAD+ metabolism is associated with aging morbidity while also being described in Double-Stranded Break (DBS) DNA Damage Repair (DDR), we have isolated and identified with distinction, pathobiochemical components of the human aging event ontology. Oncotarget. 2017 Aug 22; 8(34): 55967–55983. PLOS One .November 25, 2014https://doi.org/10.1371/journal.pone.0113939 Int J Mol Sci. 2019 Mar; 20(5): 1223. eLife 2020;9:e55828 DOI: 10.7554/eLife.55828 --- Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support
Sirtuins are protein deacetylases with multiple isoforms active in the nucleus, cytosol and mitochondria all serving unique functions and requiring NAD+. These sirtuins function to condense chromatin and yet protein abundance has less to do with potency than does the availability of NAD+ which can be synthesized from multiple routes. Furthermore, SIRT1 has been associated with antagonizing age-related decreases in the amplitudes of the SCN output obtaining age-linked differentiating phases of increases and decreases observed within a circadian cycle.. References: Int J Mol Sci. 2019 Mar; 20(5): 1223. PLOS One November 25, 2014 https://doi.org/10.1371/journal.pone.0113939 Circ Res. 2018 Sep 14; 123(7): 868–885 --- Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.13.242230v1?rss=1 Authors: Sadegh, C., Ebina, W., Arvanites, A. C., Davidow, L. S., Rubin, L. L., Macklis, J. D. Abstract: During late embryonic development of the cerebral cortex, the major class of cortical output neurons termed subcerebral projection neurons (SCPN; including the predominant population of corticospinal neurons, CSN) and the class of interhemispheric callosal projection neurons (CPN) initially express overlapping molecular controls that later undergo subtype-specific refinements. Such molecular refinements are largely absent in heterogeneous, maturation-stalled, neocortical-like neurons (termed 'cortical' here) spontaneously generated by established embryonic stem cell (ES) and induced pluripotent stem cell (iPSC) differentiation. Building on recently identified central molecular controls over SCPN development, we used a combination of synthetic modified mRNA (modRNA) for Fezf2, the central transcription factor controlling SCPN specification, and small molecule screening to investigate whether distinct chromatin modifiers might complement Fezf2 functions to promote SCPN-specific differentiation by mouse ES (mES)-derived cortical-like neurons. We find that the inhibition of a specific histone deacetylase, Sirtuin 1 (SIRT1), enhances refinement of SCPN subtype molecular identity by both mES-derived cortical-like neurons and primary dissociated E12.5 mouse cortical neurons. In vivo, we identify that SIRT1 is specifically expressed by CPN, but not SCPN, during late embryonic and postnatal differentiation. Together, these data indicate that SIRT1 has neuronal subtype-specific expression in the mouse cortex in vivo, and its inhibition enhances subtype-specific differentiation of highly clinically relevant SCPN / CSN cortical neurons in vitro. Copy rights belong to original authors. Visit the link for more info
Volume 11, Issue 26 of Oncotarget reported that in this study the authors studied the differences in mi RNA expression between sporadic and FAP-associated Desmoid tumors using microarray confirmed by quantitative PCR. Among them, mi R-133b levels were significantly lower in FAP-associated Desmoid tumors than in sporadic Desmoid tumors. The qPCR analysis showed that SIRT1 mRNA levels were significantly up-regulated in FAP-associated Desmoid tumor than in sporadic Desmoid tumor, whereas no differences in ELAVL1 expression was observed between these two Desmoid tumor types. In addition, a negative correlation was observed between mi R-133b and SIRT1 in FAP-associated Desmoid tumors, but not in sporadic Desmoid tumors The mi R-133b-SIRT1-β-catenin axis may represent a novel mechanism underlying progression of FAP-associated Desmoid tumor. Dr. Maria Teresa Rotelli from The Department of Emergency and Organ Transplantation at The University of Bari “Aldo Moro” in Bari Italy said, "Desmoid tumor (DT) is a rare, mesenchymal benign tumor, characterized by monoclonal, fibroblastic proliferation with local invasiveness, high risk of recurrence and even mortality, despite metastatization never occurs." The CNNTB1 mutations have been found in approximately 85% of DTs by routine Sanger sequencing, however, using a highly sensitive technique like next-generation sequencing, they may account for 90–95% of sporadic DT cases. In these DTs, the germline mutations in the APC gene are responsible for the nuclear accumulation of β-catenin. While the risk of death in sporadic DT is low, FAP-associated DTs are the most frequent cause of death in patients with FAP after the colon has prophylactically been removed. It must be emphasized that the disruption of the Wnt signaling represents a common pathway in both DT forms, but sporadic and FAP-associated DTs are associated with mutually exclusive molecular alterations. In a previous study, the authors have investigated a possible correlation between mi RNA expression and CTNNB1 mutations in sporadic DTs. The Rotelli Research Team concluded in their Oncotarget Research Paper that the dialog between MSCs and tumor cells in FAP-associated DT tissue microenvironment could lead to β-catenin deacetylation driven by SIRT1, promoting Wnt/β-catenin signaling cascade in this tumor. Although the number of specimens of FAP-associated DTs used in the present study was limited, it could be speculated that the β-catenin deacetylation process in FAP-associated DTs mimics the stabilization of that protein induced by CTNNB1 gene mutations occurring in sporadic DTs. Therefore, in addition to APC gene mutations, the mi R-133b-SIRT1-β-catenin axis may represent a novel mechanism underlying the progression of FAP-associated DT. However, further studies are needed to fully understand the influence of mi R-133b-SIRT1 in the genesis or progression of FAP-associated DT. DOI - https://doi.org/10.18632/oncotarget.27622 Full text - https://www.oncotarget.com/article/27622/text/ Correspondence to - Maria Teresa Rotelli - mariateresa.rotelli@uniba.it Keywords - desmoid tumor, miRNA, familial adenomatous polyposis, B-catenin, Wnt pathway About Oncotarget Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
On this episode of the Keto Kamp Podcast you will discover 9 AMAZING benefits of intermittent fasting. If you'd like health coaching from Ben Azadi, join the Keto Kamp Academy today: http://www.ketokampacademy.com // O V E R V I E W The number 1 benefit: Autophagy (self eating). Up to 70 billion cells need to be recycled each day; autophagy is the process for this to happen. An alarming stastisic about Americans, and why most are in a constant fed state, never experiencing autophagy. mTor (anabolic growth) vs autophagy (cellular breakdown and repair), and how they have an inverted relationship The problems that can occur when you are in a constant fed state The number 2 benefit: rise in stem cells. How a rise in stem cells help to heal old injuries (knee pain, back pain, etc) The number 3 benefit: A boost of ketones. How ketones protect the genes we are born with. How ketones down regulate inflammation, allowing our hormones to communicate to our cells. How ketones help you achieve the ultimate goal of metabolic flexibility. Why ketones are a cleaner fuel source than glucose (firewood vs gas stove analogy) The keto diet turns on the SIRT1 longevity gene Keto diet is 70% fat but that can Come from body fat You can choose where you want your next meal to come from, your plate of food or butts and thighs The number 4 benefit: Energy diversion for healing How fasting provides you with energy and blood flow to heal the body, and crush the day. The body will heal old injuries. Talk about the autophagy pain I had during a 5 day water fast. Stem cells Number 5: Increased brain function and mental focus, increase in BDNF The number 6 benefit: Hormone optimization. How our hormones and our cells communicate, and why having more sensitive hormones through fasting has amazing benefits for us. How inflammation through being in a constant fed state creates cellular inflammation, and results in our hormones not being able to communicate to our cells. Why we don't have a lack of hormones problem, we have an inflammation problem. The number 7 benefit: Resets the microbiome. The problem of leaky gut, and how fasting gives your digestive system a break. Study by Dr. Zach Bush which showed it took 14 hours to digest a standard American diet meal. How a compromised digestive system doesn't allow the nutrition you eat to be assimilated properly. The number 8 benefit: Resets the DNA, turns off bad genes. How genes work, and how we control them. Number 9 benefit: fat loss, reversing insulin resistance. How to practice fasting. 1: get keto adapted. 2: don’t eat 3 hours before bed, and 3 hours after waking up. 3: 18/6 schedule on a consistent basis // R E S O U R C E S ➡️Check out this keto beginners kit: http://www.ketokampkit.com
David A. Sinclair, Ph.D., A.O. is a Professor in the Department of Genetics at Harvard Medical School. He is best known for his work on understanding why we age and how to slow its effects. His research has been primarily focused on the sirtuins, protein-modifying enzymes that respond to changing NAD+ levels and to caloric restriction (CR) with associated interests in chromatin, energy metabolism, mitochondria, learning and memory, neurodegeneration, and cancer. The Sinclair lab was the first one to identify a role for NAD+ biosynthesis in regulation of lifespan and first showed that sirtuins are involved in CR in mammals. They first identified small molecules that activate SIRT1 such as resveratrol and studied how they improve metabolic function using a combination of genetic, enzymological, biophysical and pharmacological approaches. They recently showed that natural and synthetic activators require SIRT1 to mediate the in vivo effects in muscle and identified a structured activation domain. They demonstrated that miscommunication between the mitochondrial and nuclear genomes is a cause of age-related physiological decline and that relocalization of chromatin factors in response to DNA breaks may be a cause of aging. Time stamps: 9:35 Start of podcast. 10:53 Does when you eat matter more than what you eat? 12:48 Time restricted feeding and longevity. 17:04 What causes us to age? 20:05 What cellular information is being lost? 26:35 What Causes DNA break? 28:47 DNA breaks as clastogenesis. 29:32 Food and DNA breaks 31:28 PARP enzymes. 34:57 NAD 40:15 NAMPT 42:35 Nicotinamide and sirtuins. 44:25 Methylation and methyl groups. 45:44 Sirtuins. 48:11 Heat/cold and sirtuins/NAMPT 52:54 What do sirtuins do with ADP ribose. 56:15 Role of active sirtuins. 58:25 Other longevity genes. 1:04:30 Importance of mitochondrial NAD levels. 1:05:50 Ketosis and NAD. 1:11:20 Resveratrol. 1:14:45 Xenohormesis and plant molecules- my view vs David’s 1:19:55 Resveratrol trials, concerns about resveratrol. 1:26:05 mTOR 1:31:37 David's plant based diet- and why it could be better 1:38:10 Meat consumption and the environment 1:45:35 Where to find David's stuff. 1:47:20 The most radical thing David has done recently. David’s contact info: https://genetics.med.harvard.edu/sinclair/people/sinclair.php https://lifespanbook.com/ Instagram: @davidsinclairphd Twitter: @davidasinclair My info PATREON: https://www.patreon.com/paulsaladinomd Ancestral Supplements https://ancestralsupplements.com/ Code SALADINOMD on the shopify site to receive 10% off. Use the code CARNIVOREMD at www.whiteoakpastures.com all month for 10% off your order! Use CARNIVORE15 for 15% off special deals this week at info.whiteoakpastures.com/carnivoremd JOOVV: www.joovv.com/paul Native: For 20% off your first purchase, visit nativedeodorant.com and use promo code SALADINO during checkout! INSIDER: carnivoremd.com My contact information: SOCIAL MEDIA Instagram: @carnivoremd Website: carnivoremd.com Twitter:@carnivoremd Facebook: Paul Saladino MD email: drpaul@carnivoremd.com Stay Radical!
In this episode, we’ll talk about 7 amazing benefits of fasting. 7 Week Beyond Fasting Program w/ Ben Azadi: http://www.ketokampfasting.com Get my FREE Keto Kickstart Guide: http://www.ketokickstartguide.com My Favorite Keto Beef Jerky & More: http://www.paleovalley.com Use coupon code ketokamp10 for 10% off Here is an overview of this episode: The number 1 benefit: Autophagy (self eating). Up to 70 billion cells need to be recycled each day; autophagy is the process for this to happen. How autophagy works (refrigerator analogy) An alarming stastisic about Americans, and why most are in a constant fed state, never experiencing autophagy. mTor (anabolic growth) vs autophagy (cellular breakdown and repair), and how they have an inverted relationship The problems that can occur when you are in a constant fed state The number 2 benefit: rise in stem cells. How a rise in stem cells help to heal old injuries (knee pain, back pain, etc) The number 3 benefit: A boost of ketones. How ketones protect the genes we are born with. How ketones down regulate inflammation, allowing our hormones to communicate to our cells. How ketones help you achieve the ultimate goal of metabolic flexibility. Why ketones are a cleaner fuel source than glucose (firewood vs gas stove analogy) The keto diet turns on the SIRT1 longevity gene The number 4 benefit: Energy diversion. How fasting provides you with energy and blood flow to heal the body, and crush the day. Study by Dr. Zach Bush which showed it took 14 hours to digest a standard American diet meal. The number 5 benefit: Hormone optimization. How our hormones and our cells communicate, and why having more sensitive hormones through fasting has amazing benefits for us. How inflammation through being in a constant fed state creates cellular inflammation, and results in our hormones not being able to communicate to our cells. Why we don't have a lack of hormones problem, we have an inflammation problem. The number 5 benefit: Resets the microbiome. The problem of leaky gut, and how fasting gives your digestive system a break. How a compromised digestive system doesn't allow the nutrition you eat to be assimilated properly. The number 7 benefit: Resets the DNA, turns off bad genes. How genes work, and how we control them. // R E S O U R C E S 7 Week Beyond Fasting Program w/ Ben Azadi: http://www.ketokampfasting.com Get my FREE Keto Kickstart Guide: http://www.ketokickstartguide.com LowCarb USA Boca Raton, Florida January 2020 conference: https://www.lowcarbusa.org/low-carb-events/se-2020/ Use KetoKamp at checkout for $100 off your ticket price. YouTube Channel: www.youtube.com/ketokamp Beyond Fasting book by Dr. Daniel Pompa: http://bit.ly/2XhbZQh [VIDEO] 7 Amazing Benefits of Fasting: https://www.youtube.com/watch?v=cAoHwdYDjec [VIDEO] 13 Ways to Boost Autophagy Without Fasting: https://www.youtube.com/watch?v=I6lxK3NJpEA My Favorite Keto Coffee Blend: http://www.ketokampblend.com My Favorite Keto Beef Jerky & More: http://www.paleovalley.com Use coupon code ketokamp10 for 10% off Join The Keto Kamp Inner Circle: https://www.ketokamp.com YouTube Channel: www.youtube.com/ketokamp This podcast is for information purposes only. Statements and views expressed on this podcast are not medical advice. This podcast including Ben Azadi disclaim responsibility from any possible adverse effects from the use of information contained herein. Opinions of guests are their own, and this podcast does not accept responsibility of statements made by guests. This podcast does not make any representations or warranties about guests qualifications or credibility. Individuals on this podcast may have a direct or non-direct interest in products or services referred to herein. If you think you have a medical problem, consult a licensed physician.
In this episode, we’ll talk about 6 surprising benefits of ketones. Get my FREE Keto Kickstart Guide: http://www.ketokickstartguide.com My Favorite Keto Coffee Blend: http://www.ketokampblend.com Here is an overview of this episode: The #1 surprising benefit of ketones: It raises growth hormone, protects all cells & DNA from oxidative stress Why our cells love fat (ketones) and how they protect our genes The #2 surprising benefit of ketones: Ketones reduce inflammation and its markers Which blood markers to look at for inflammation in the body How ketones down regulate cellular inflammation, allowing fat burning hormones to get into the cell and burn fat The #3 surprising benefit of ketones: Ketones protect and repair the inner mitochondria of the cell, and helps the cells body become fat adapted (metabolic flexibility) The importance of achieving metabolic flexibility The #4 surprising benefit of ketones: It increases cellular energy The role of mitochondria and ATP within our cells How increasing cellular energy reduces the risk of disease The #5 surprising benefit of ketones: It supercharges your brain, providing 3x more energy than glucose How burning glucose (sugar) as the primary fuel source is a toxic fuel source that ages us faster vs ketones that burns very clean The #6 most surprising benefit of ketones: It turns on the SIRT1 gene which extends life How ketones protect our telomeres which is the most accurate way to determine how long someone will live As we age it gets more difficult to active this SIRT1 longevity gene Get my FREE Keto Kickstart Guide: http://www.ketokickstartguide.com LowCarb USA Boca Raton, Florida January 2020 conference: https://www.lowcarbusa.org/low-carb-events/se-2020/ Use KetoKamp at checkout for $100 off your ticket price. YouTube Channel: www.youtube.com/ketokamp [VIDEO] 6 Surprising Benefits of Ketones: https://www.youtube.com/watch?v=haR43YnSY9k My Favorite Keto Coffee Blend: http://www.ketokampblend.com My Favorite Keto Beef Jerky & More: http://www.paleovalley.com Use coupon code ketokamp10 for 10% off // R E S O U R C E S Beyond Fasting book by Dr. Daniel Pompa: http://bit.ly/2XhbZQh Telomeres Testing Kit | TeloYears: http://bit.ly/2ZFFRSJ Join The Keto Kamp Inner Circle: https://www.ketokamp.com Get the Keto Kickstart Guide for FREE: http://www.ketokickstartguide.com YouTube Channel: www.youtube.com/ketokamp My Favorite Keto Beef Jerky & More: http://www.paleovalley.com Use coupon code ketokamp10 for 10% off This podcast is for information purposes only. Statements and views expressed on this podcast are not medical advice. This podcast including Ben Azadi disclaim responsibility from any possible adverse effects from the use of information contained herein. Opinions of guests are their own, and this podcast does not accept responsibility of statements made by guests. This podcast does not make any representations or warranties about guests qualifications or credibility. Individuals on this podcast may have a direct or non-direct interest in products or services referred to herein. If you think you have a medical problem, consult a licensed physician.
Researcher Jon Ramsey, PhD is Professor in the Department of Molecular Biosciences within the School of Veterinary Medicine at UC Davis. His study of animals focuses on nutrition as it relates to obesity and aging. The goal of his research is to understand the biological mechanisms that contribute to the aging process and to develop dietary interventions that promote healthy aging and weight loss. In this podcast, NBT Scientific Director Megan Roberts interviews Dr. Ramsey about his research in the area of calorie restriction and its beneficial effects on longevity and healthspan. They examine the scientific literature on energy and macronutrient restriction, including some of the possible biological mechanisms driving the anti-aging effects of these interventions. They also discuss what this all means in practical terms for those seeking optimal health as they age. Here’s the outline of this interview with Jon Ramsey: [00:01:35] Calorie restriction for increasing lifespan. [00:02:01] Theories of aging. [00:04:40] Osborne and Mendel; Study: Osborne, Thomas B., Lafayette B. Mendel, and Edna L. Ferry. "The effect of retardation of growth upon the breeding period and duration of life of rats." Science 45.1160 (1917): 294-295. [00:04:58] Clive McCay; Studies: McCay, Clive Maine, and Mary F. Crowell. "Prolonging the life span." The Scientific Monthly 39.5 (1934): 405-414 and McCay, Carl M., Mary F. Crowell, and Lewis A. Maynard. "The effect of retarded growth upon the length of life span and upon the ultimate body size: one figure." The journal of Nutrition 10.1 (1935): 63-79. [00:06:25] Calorie restriction literature in animals. [00:07:39] Types of rodents studied. [00:08:09] Comparing effect of caloric restriction (CR) on different strains of mice; Study: Liao, Chen‐Yu, et al. "Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening." Aging cell 9.1 (2010): 92-95. [00:09:08] Time restricted feeding in animal models. [00:11:51] Calorie restriction vs. malnutrition. [00:12:00] Different levels of calorie restriction. Study: Weindruch, Richard, et al. "The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake." The Journal of nutrition 116.4 (1986): 641-654. [00:13:36] Effects of 10% dietary restriction: Richardson, Arlan, et al. "Significant life extension by ten percent dietary restriction." Annals of the New York Academy of Sciences 1363.1 (2016): 11-17. [00:15:09] CALERIE study and resulting Publications. [00:17:56] Analyses of CALERIE data. Studies: Belsky, Daniel W., et al. "Change in the rate of biological aging in response to caloric restriction: CALERIE Biobank Analysis." The Journals of Gerontology: Series A 73.1 (2017): 4-10. and Redman, Leanne M., et al. "Metabolic slowing and reduced oxidative damage with sustained caloric restriction support the rate of living and oxidative damage theories of aging." Cell metabolism 27.4 (2018): 805-815. [00:19:21] Dietary restriction and oxidative stress; Study: Walsh, Michael E., Yun Shi, and Holly Van Remmen. "The effects of dietary restriction on oxidative stress in rodents." Free Radical Biology and Medicine 66 (2014): 88-99. [00:20:29] Podcast: How Oxidative Stress Impacts Performance and Healthspan, with Megan Roberts. [00:20:40] Effects of CR on reactive oxidative species production; Study: Ramsey, Jon J., Mary-Ellen Harper, and Richard Weindruch. "Restriction of energy intake, energy expenditure, and aging." Free Radical Biology and Medicine 29.10 (2000): 946-968. [00:20:59] Effects of fasting on the liver; Study: Salin, Karine, et al. "Decreased mitochondrial metabolic requirements in fasting animals carry an oxidative cost." Functional Ecology (2018). [00:21:56] Control of food intake: Do animal models accurately reflect human behavior? [00:25:06] Enriched environment; Study: McMurphy, Travis, et al. "Implementation of environmental enrichment after middle age promotes healthy aging." Aging (Albany NY) 10.7 (2018): 1698. [00:26:16] Monkey studies; Study: Ramsey, J. J., et al. "Dietary restriction and aging in rhesus monkeys: the University of Wisconsin study." Experimental gerontology 35.9-10 (2000): 1131-1149. [00:26:35] University of Wisconsin study: Colman, Ricki J., et al. "Caloric restriction delays disease onset and mortality in rhesus monkeys." Science 325.5937 (2009): 201-204. [00:26:35] National Institute on Aging study: Mattison, Julie A., et al. "Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study." Nature 489.7415 (2012): 318. [00:31:34] Biological mechanisms behind the beneficial effects of CR. [00:33:09] Central metabolism sensors. [00:35:28] Mitochondrial proton leak. [00:37:41] Study: Bevilacqua, Lisa, et al. "Effects of short-and medium-term calorie restriction on muscle mitochondrial proton leak and reactive oxygen species production." American Journal of Physiology-Endocrinology and Metabolism 286.5 (2004): E852-E861. [00:40:59] The influence of dietary fat source; Study: Villalba, José Manuel, et al. "The influence of dietary fat source on liver and skeletal muscle mitochondrial modifications and lifespan changes in calorie-restricted mice." Biogerontology 16.5 (2015): 655-670. [00:42:16] Effects of protein restriction on longevity; Studies: 1. Davis, Teresa A., Connie W. Bales, and Roy E. Beauchene. "Differential effects of dietary caloric and protein restriction in the aging rat." Experimental gerontology 18.6 (1983): 427-435; 2. Pugh, Thomas D., Roger G. Klopp, and Richard Weindruch. "Controlling caloric consumption: protocols for rodents and rhesus monkeys☆." Neurobiology of aging 20.2 (1999): 157-165. [00:42:23] More recent studies on protein restriction: 1. Pamplona, Reinald, and Gustavo Barja. "Mitochondrial oxidative stress, aging and caloric restriction: the protein and methionine connection." Biochimica Et Biophysica Acta (BBA)-Bioenergetics 1757.5-6 (2006): 496-508; 2. Caro, Pilar, et al. "Effect of 40% restriction of dietary amino acids (except methionine) on mitochondrial oxidative stress and biogenesis, AIF and SIRT1 in rat liver." Biogerontology 10.5 (2009): 579-592. [00:43:42] Morris Ross study: Ross, Morris H. "Length of life and nutrition in the rat." The Journal of nutrition 75.2 (1961): 197-210. [00:44:03] Effects of dietary lipid composition on lifespan; Study: López-Domínguez, José A., et al. "The influence of dietary fat source on life span in calorie restricted mice." Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences 70.10 (2014): 1181-1188. [00:45:07] Anthony J. Hulbert. [00:48:46] Omega-3 study: Aung, Theingi, et al. "Associations of omega-3 fatty acid supplement use with cardiovascular disease risks: meta-analysis of 10 trials involving 77 917 individuals." JAMA cardiology 3.3 (2018): 225-234. [00:50:02] Ketogenic Diets. [00:50:05] Study: Roberts, Megan N., et al. "A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice." Cell Metabolism 26.3 (2017): 539-546. Podcast: A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice, with Megan (Hall) Roberts. [00:53:47] Intermittent fasting study: Mitchell, Sarah J., et al. "Daily fasting improves health and survival in male mice independent of diet composition and calories." Cell metabolism(2018). [00:54:19] Valter Longo, PhD. [00:54:49] Weight cycling; Study: Smith Jr, Daniel L., et al. "Weight cycling increases longevity compared with sustained obesity in mice." Obesity 26.11 (2018): 1733-1739. [00:55:22] Exercise in the context of carb restriction and longevity. [00:56:08] Study: Holloszy, John O., et al. "Effect of voluntary exercise on longevity of rats." Journal of applied physiology 59.3 (1985): 826-831. [00:58:41] Take home points. [01:01:08] With unlimited resources, what would you study? [01:02:08] Jon Ramsey, PhD at UC Davis.
This week's guest is Dr Ross Grant, a clinical professor of medicine at Sydney Adventist in Sydney, Australia. He is considered one of the world's foremost authorities on NAD+ science and therapeutics. Fair warnings: this episode is deeply technical and scientific, but during the last 15 minutes of the interview Dr Grant speculates on how NAD+ might be beneficial directly to Alzhiemer's (and Parkinson's patients). ALSO, we apologize for the sound quality of this episode. we are working to bring you better quality sound with each episode. NAD+ or Nicotinamide Adenine Dinucleotide is a molecule necessary for a huge number of biological processes supporting human life. NAD+ levels decrease as we age. The body produces NAD+, but in addition to the natural decline in production, as we age there is also likely an increased need for NAD+ that is beyond our bodies ability to produce. Key Biologic Processes where NAD+ is involved Repair of the DNA (single base pairs) via PARP (Poly-ADP ribose polymerase) Energy Production Enzymes Redox-Repair Enzymatic activity Epigenetical Switch - controlling gene expression especially of SIRT1 activity. Immune system regulation/repair - especially relevant in Alzheimers where the immune systems and inflammation appear to be overactive making self repair more difficult. Activate Tankyrase in order to extend telomeres. It may act as a direct neurotransmitter in the brain and nervous system. In an aging brain, inflammation and susceptibility to oxidative stress increase. As this happens, NAD+ levels drop and the brain loses NAD+'s sponsorship of longevity genes and mitochondrial support via sirtuin activity all contributing to eventual cell death. Taking or using an outside source of NAD+ seems less likely to help someone if they have a lot of free radical damage (super oxide activity where oxygen free radicals are doing damage) occurring. Caloric Restriction is one of the only scientifically proven methods to reduce damage from oxidative stress. When there is excess caloric intake (i.e. eating too much) or eat poor quality food our usable NAD+ is "tied up" in a less usable form called NADH. Intake of excess and/or poor quality calories (i.e. bad food) gives rise to excess free radicals in the body. This occurs as cell turnover and reproduce themselves over time. Each "generation" of cells in our bodies (sometimes just hours or days later) will be made with increasing damage from these free radicals being made from a poor diet, so when this generation of cells is produced they are produced as damaged goods and effectively tie up NAD+. This increasing injury over time is known as "aging" and it depletes the body of its usable NAD+. SIRT1 - Sirtuin (Silent Information Regulators) are able to switch on and off genes, including those that produce anti-oxidant capabilities in the body. When the body gets too many calories or the wrong kind of calories these genes - through an epigenetic mechanism known as acetylation - get down shifted and aren't able to protect us like they are designed to because the NAD+ and materials that turn them on are "busy" (ie they take the form of NADH). Being busy renders them unable to "hit the activation switch" as it were. In general, mitochondria (energy producing parts of cells) seem to function less efficiently over time (ie aging). Some of the earliest changes in Alzheimer's occur in the mitochondria. The brain has an inordinate number of mitochondria relative to the rest of the body. NAD picks up electrons through a mitochondrion in a fairly efficient way to create energy currency in the body. Over time, this process can breakdown and become "leaky." Nutrient rich, energy limited diets (healthy, modest portions) seems to be one way to minimize these inefficiencies over time (i.e caloric restriction). Mitochondrial Biogenesis -is the process of adding mass and function to the mitochondria (energy producing parts of our cells). Mitochondria are known to "crash" and are susceptible to damage early on in Alzheimer's. You can increase available NAD by increasing the bodies production of NAD 1) from Tryptophan 2) from over the counter forms of NAD. Practically- these 3 forms can be bought over the counter: 1) Nicotinamide Riboside 2) Nicotinamide mononucleotide 3) Niacin Dr Grant mentioned about 350mg may be a responsible dose, but also cautioned that some oral forms of Nicotinamide may end up stacking up and having the opposite effects that are intended (eg blocking sirtuin and PARP pathways), so you will - as always - definitely want to consult with your healthcare practitioner before trying this. Each one of these three forms can increase the NAD inside our cells. But just supplementing with NAD without addressing other lifestyle factors of a good diet, proper sleep, enough exercise and stress reduction can lead to a build up of a recycling chemical in the body called, homocysteine which is associated with Alzheimer's, heart disease and other health issues. Currently, there are only a few research institutions in the world that can truly measure NAD. It is unfortunately not widely available outside a research setting. According to Dr Grant, Dr Charles Brenner lab at the University of Iowa is the most reliable in the United States IV (intravenous) NAD+ is being administered through a variety of clinical outlets in the US under medical supervision. This might be the most useful way to use it in neurodegenerative diseases like Alzheimer's and Parkinson's. To learn more about NAD+ https://medicalsciences.med.unsw.edu.au/people/dr-ross-grant http://www.springfieldwellnesscenter.com/ http://www.nadtreatmentcenter.com/nad-research/
Tommy and I recorded this interview in person at the Buck Institute for Research on Aging where we were attending Dr. Dale Bredesen’s training for reversing cognitive decline. If you’ve yet to discover Dr. Bredesen’s amazing work, I’d highly recommend his STEM-Talk interview. My attempt to capture the impressiveness of the Buck Institute leaves a lot to be desired, but since I promised a photo during the recording, here it is: We love our supplements at Nourish Balance Thrive, and we regularly recommend them to the people we work with, usually when indicated by a test result. What we’re less keen on is expensive nonsense with no human data or even plausible mechanism of action. Oxaloacetate falls into this category, and in this interview, you'll learn enough biochemistry to understand why you should save your money. As always, we reserve the right to be proven wrong! In the second part of this interview, you'll learn about why it's essential to eat to fuel for your activity. We're huge fans of a ketogenic diet for a handful of very specific applications, but not as a general recommendation, especially for athletes engaging in highly glycolytic activities like Crossfit and obstacle course racing. Here’s the outline of this interview with Dr. Tommy Wood, MD PhDc: [00:00:26] Buck Institute for Research on Aging. [00:00:43] Bredesen, Dale E., et al. "Reversal of cognitive decline in Alzheimer's disease." Aging (Albany NY) 8.6 (2016): 1250. [00:00:59] Journal of Neuroscience. [00:02:00] Hippocampal volume increasing. [00:02:26] Blood chem, genotyping, biotoxins, heavy metals. [00:02:32] ReCode software. [00:03:17] Send me your questions for Dr. Bredesen. [00:03:41] Oxaloacetate supplementation. [00:04:01] How to Achieve Near-Normal Blood Sugar with Type 1 Diabetes with Dr. Keith Runyan, MD. [00:05:18] Caloric restriction in humans. [00:05:23] CALERIE trial. [00:06:08] Calorie restriction falters in the long run. [00:07:01] The benefit comes on the refeed. [00:07:14] Valter Longo, Ph.D. on Fasting-Mimicking Diet & Fasting for Longevity, Cancer & Multiple Sclerosis. [00:07:41] Getting Stronger with Todd Becker. [00:08:18] C. elegans. [00:08:47] Malate-aspartate shuttle. [00:09:20] NAD+/NADH ratio. [00:09:32] AMP-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1). [00:09:45] FOXO3. [00:10:01] Nicotinamide riboside (NR). [00:10:19] Strong, Randy, et al. "Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on life span of genetically heterogeneous mice." The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 68.1 (2013): 6-16. [00:11:14] Toxic effects of glutamate. [00:11:48] Excitotoxicity. [00:12:30] Aspartate transaminase (AST) on a blood chem. [00:13:37] The OAA supplements include a meaningless dose anyway. [00:14:17] Anaplerotic reactions. [00:15:27] Pyruvate dehydrogenase and biotin (B7) deficiency. [00:16:54] Context for a ketogenic diet. [00:18:06] Glycolytic activity. [00:19:20] Fasting blood glucose. [00:19:36] Alkaline phosphatase (Alk Phos). [00:20:01] Zinc deficiency. [00:21:26] Thyroid. [00:22:02] Deiodinase enzymes. [00:24:11] Lipids. [00:24:39] LDL receptor. [00:25:29] Red blood cell production [00:25:51] Mean corpuscular volume (MCV). [00:26:33] Macrocytosis due to folate deficiency. [00:29:24] Masharani, U., et al. "Metabolic and physiologic effects from consuming a hunter-gatherer (Paleolithic)-type diet in type 2 diabetes." European journal of clinical nutrition 69.8 (2015): 944-948. [00:31:07] Ketosis makes you sharp so you can go get some food. [00:31:46] A New Hope for Brain Tumors with Dr. Adrienne Scheck. [00:31:59] Dominic D'Agostino: Researcher and Athlete on the Benefits of a Ketogenic Diet. [00:32:08] A ketogenic diet shows some promise for Multiple Sclerosis and Alzheimer’s. [00:32:33] Light dark cycles. [00:33:18] Breast feeding and carbs. [00:33:45] Thompson, Betty J., and Stuart Smith. "Biosynthesis of fatty acids by lactating human breast epithelial cells: an evaluation of the contribution to the overall composition of human milk fat." Pediatr Res 19.1 (1985): 139-143. [00:34:05] Babies are in ketosis. [00:34:32] Medium-chain triglyceride. [00:35:07] Read, W. W. C., PHYLLIS G. LUTZ, and ANAHID TASHJIAN. "Human Milk Lipids II. The influence of dietary carbohydrates and fat on the fatty acids of mature milk. A study in four ethnic groups." The American journal of clinical nutrition 17.3 (1965): 180-183. [00:35:21] Keto rat experiment.
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 18/19
Chronic obstructive pulmonary disease (COPD) is characterized by an irreversible loss of lung function and is one of the most prevalent and severe diseases world-wide. A major feature of COPD is emphysema- a long-term, progressive condition. The hallmark of emphysema includes the destruction of alveolar structures leading to enlarged air spaces and reduced surface area. Experimental evidence suggests that emphysema development is driven by accelerated senescence of lung cells but the underlying mechanism of senescence is yet to be fully elucidated. Protein arginine methyltransferases (PRMTs) are important for cellular processes, such as the regulation of senescence, cell proliferation, differentiation and apoptosis. The PRMT family includes 11 members classified as type I, II or III enzymes depending on their methylation pattern (asymmetric dimethylation, symmetric dimethylation or monomethylation, respectively). One member of this family is PRMT4, a type I enzyme, which is also called coactivator associated arginine methyltransferase 1 (CARM1). It was originally identified as a coactivator for steroid hormone receptors. CARM1 is known to methylate histone H3 and various non-histone proteins that play essential roles in transcriptional regulation, RNA splicing, and metabolism. Most importantly, complete loss of CARM1 leads to disrupted differentiation and maturation of alveolar epithelial type-II cells (ATII). Furthermore, CARM1 also plays a role in regulating cellular senescence via CARM1-dependent methylation. Based on these reports, we hypothesized that CARM1 regulates the development and progression of emphysema. To address this, we investigated the contribution of CARM1 to alveolar rarefication using the mouse model of elastase-induced emphysema in vivo and siRNA-mediated knockdown in ATII-like LA4 cells in vitro. We monitored emphysema progression for 161 days in mice treated with a single oropharyngeal application of elastase. The progression was manifested by the decline in lung function parameters. The mean chord length (Lm) confirmed a time dependent airspace enlargement and was directly correlated with a significant increase in dynamic lung compliance. We also observed that at later time points (day 56 and 161), emphysema progression was inflammation-independent. We demonstrated that emphysema advancement was associated with a time-dependent downregulation of CARM1, specifically in alveolar epithelial cells. Furthermore, the global CARM1 activity was also reduced as reflected by an elevated level of CARM1 phosphorylation in the lung. Most importantly, elastase-treated CARM1 haploinsufficient mice showed significantly increased airspace enlargement (52.5±9.6 µm vs. 38.8±5.5 µm, p
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 05/06
Tue, 24 Jun 2014 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/17112/ https://edoc.ub.uni-muenchen.de/17112/1/Monteserin_Garcia_Jose_Luis.pdf Monteserin Garcia, Jose Luis ddc:570, ddc:500, Fakultät
Summer loving is in the air, so what better time to think about sex? But we're not going to get graphic - we're talking about the genetics of sex determination. Plus, why turkeys need a wingman, figuring out fingerprints, and a leggy gene of the month. Like this podcast? Please help us by supporting the Naked Scientists
© 2020-2025 Ivy Podcast Discovery LLC
