Podcasts about sasp

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Best podcasts about sasp

Latest podcast episodes about sasp

Divas puslodes
Kanādas parlamenta vēlēšanās uzvar liberāļi. Pieaug saspīlējums starp Indiju un Pakistānu

Divas puslodes

Play Episode Listen Later Apr 30, 2025 53:55


Kanādas parlamenta vēlēšanās uzvar liberāļi. Pieaug saspīlējums starp Indiju un Pakistānu. Latvija vienīgā kandidāte no Austrumieronas ANO Drošības padomē. Aktualitātes analizē Latvijas Radio ārzemju ziņu korespondents Rihards Plūme un laikraksta "Diena" komentētājs Andis Sedlenieks. Kanādas liberāļi – par mata tiesu no triumfa 28. aprīlī notikušo Kanādas Parlamenta Pārstāvju palātas vēlēšanu rezultāti, salīdzinot ar priekšvēlēšanu aptauju rādītājiem, īpaši nepārsteidz. Liberālā partija, kopš janvāra nogales piedzīvojusi strauju popularitātes kāpumu, ieguvusi vēlēšanās labāko rezultātu. Iemesls ir ne tikai ilggadējā premjera un liberāļu līdera Džastina Trudo prašanās savlaicīgi aiziet no politiskās avanscēnas, bet arī „Trampa faktors”. Vašingtonas varasvīra šokējošā izrunāšanās par plāniem anektēt Kanādu un kaimiņvalsts eksporta aplikšana ar tarifiem ir saniknojusi kanādiešus, un pretošanās noskaņojums kļuva par jaunā premjera Marka Kārnija vadīto liberāļu priekšvēlēšanu kampaņas vadmotīvu. Nevar gan sacīt, ka trampismam tuvu noskaņu esamība liberāļu galveno konkurentu – Konservatīvās partijas – platformā būtu nākusi šim spēkam ļoti par sliktu. Konservatīvajiem izdevies gūt vairāku desmitgažu laikā izcilāko rezultātu un pieaudzēt mandātu skaitu pat vairāk nekā liberāļiem. Tiesa, deputāta mandāts iet secen konservatīvo līderim Pjēram Pualjēvram. Galvenais zaudētājs šajā situācijā izrādījusies mēreni kreisā Jaunā demokrātiskā partija, kuras frakcija sarukusi par vairāk nekā divām trešdaļām. Partijas līderis Džagmīts Singhs jau paziņojis par atkāpšanos no amata. Trešdaļu mandātu zaudējusi arī frančvalodīgo kanādiešu partija Kvebekas bloks. Tā nu liberāļiem, pēc visa spriežot, pietrūks vien trīs balsu no simt septiņdesmit divām, lai veidotu vairākuma valdību, un, tāpat kā pāris iepriekšējos sasaukumos, arī šajā Kanādai būs mazākuma valdība, kuras atrašanos pie varas noteiks mazāko partiju atbalsts valdošajai. Kvebekas bloka līderis Īvs Fransuā Blanšē aicinājis visus politiskos spēkus vienoties par „pamieru”, kamēr valsts tiek cauri pašreizējiem nestabilajiem laikiem. Kāpēc Latvija grib, bet Melnkalne – nē? Šī gada jūnijā Apvienoto Nāciju Organizācijas Ģenerālā asambleja, kā ik gadu, balsos par piecu jaunu ANO Drošības padomes locekļu apstiprināšanu. Kā zināms, kopumā šai ANO institūcijā darbojas piecpadsmit valstis, no kurām piecas – Savienotās Valstis, Ķīna, Krievija, Lielbritānija un Francija – ir pastāvīgie locekļi, savukārt atlikušās desmit periodiski mainās. Pie tam katram planētas reģionam Drošības padomē rezervēts noteikts vietu skaits. Vienu no divām Austrumeiropas vietām ieņem pastāvīgā locekle Krievija, savukārt uz otru, kuru šajā reizē atbrīvos Slovēnija, pretendē Latvija. Otra sākotnējā pretendente – Melnkalne – savu pieteikumu pirms pāris mēnešiem atsauca. Kā intervijā Melnkalnes laikrakstam „Vijesti” izteicies ārlietu ministrs Ervins Ibrahimovičs, tāds lēmums pieņemts, jo Melnkalnei šobrīd jākoncentrē visi spēki virzībai uz iestāšanos Eiropas Savienībā, kam darbošanās Drošības padomē var nenākt par labu. Drošības padome ir vienīgā no ANO struktūrām, kura ir pilnvarota izdot dalībvalstīm saistošas rezolūcijas; visām pārējām ANO ietvaros izdotajām rezolūcijām ir rekomendējošs raksturs. Piecu pastāvīgo locekļu statuss ar veto tiesībām saglabājies kopš organizācijas radīšanas Otrā pasaules kara izskaņā, un lielā mērā atspoguļo tā laika ģeopolitisko realitāti, kad galvenās pasaules kara uzvarētājas nodrošināja sev īpašu statusu. Kopš tā laika daudz kas mainījies, un jau vismaz vairākas desmitgades četras valstis – Indija, Brazīlija, Japāna un Vācija – izvirza pretenzijas uz Drošības padomes pastāvīgā locekļa statusu, ciktāl Japāna un Vācija sniedz ļoti nozīmīgu finansiālo ieguldījumu Apvienoto Nāciju darbībā, savukārt Indija un Brazīlija aktīvi piedalās ANO militārajās misijās. Tomēr ir vesela grupa pietiekami ietekmīgu valstu, kuras šādai paplašināšanai pretojas. Kopš Krievijas pilna mēroga iebrukuma Ukrainā arvien skaļāk izskan viedoklis, ka agresorvalsts savu īpašo statusu Drošības padomē nav pelnījusi. Krievijas Federācija kā tāda nekad nav tikusi ievēlēta par pastāvīgo locekli, bet gan ir mantojusi šo statusu no tās priekšgājējas Padomju Savienības. Indija un Pakistāna – milžu rīvēšanās Jau vairāk nekā trīs gadu desmitus Indijas Džammu un Kašmiras pavalstī nenorimst bruņota pretestība valsts centrālajai varai. Savulaik šais zemēs pastāvēja pusneatkarīga monarhija ar ticības ziņā neviendabīgu iedzīvotāju sastāvu, un tad, kad 1947. gadā kādreizējās Britu Indijas vietā tapa Indijas un Pakistānas valstis, kuru pamatā bija iedzīvotāju reliģiskā piederība, Džammu un Kašmira kļuva par strīdus ābolu. Pagājušā gadsimta astoņdesmitajos gados islāma kaujinieki, kuri cīnās par provinces pievienošanu Pakistānai, sāka piekopt terora metodes. Vienu šādu asiņainu ekscesu Indija piedzīvoja 22. aprīlī, kad vairāki ar automātiskajiem ieročiem bruņoti vīri ieradās tūristu iecienītā lokācijā, vispirms atklāja haotisku uguni, pēc tam nošķīra atsevišķi vīriešus un sāka noskaidrot viņu reliģisko piederību. Tos, kuri nebija apgraizīti un nezināja arī norunāt Dienvidāzijā populāru islāma lūgšanas frāzi, nošāva. Pavisam dzīvību zaudēja 26 cilvēki, starp kuriem bija arī viens Nepālas pavalstnieks un viens vietējais iedzīvotājs, musulmanis, kurš mēģināja nepieļaut izrēķināšanos. Šis ir asiņainākais terora akts Indijā kopš 2008. gada islāma teroristu uzbrukumiem Mumbajā. Sākotnēji atbildību par 22. aprīļa slaktiņu uzņēmās kaujinieku organizācija „Pretestības fronte”, kura gan dažas dienas vēlāk savu paziņojumu atsauca. Savukārt Indijas varasiestādes jau nākamajā dienā pēc notikušā paziņoja, ka saziņa rādot teroristu saistību ar Pakistānas slepenajiem dienestiem. Indija izraidīja vairākus Pakistānas diplomātus un atsauca savējos no Islāmābādas, slēdza sauszemes robežu, anulēja vīzas daļai Pakistānas pilsoņu un pārtrauca izsniegt jaunas. Sevišķi nopietni tiek uzlūkota Indas ūdeņu vienošanās darbības apturēšana. 1960. gadā noslēgtā starpvalstu vienošanās regulē Indas upes un vairāku tās pieteku ūdens resursu izmantošanu. Upju iztekas atrodas Indijā, bet galvenā ūdeņu izlietotāja ir Pakistāna, sevišķi lauksaimniecībai, kas veido gandrīz ceturto daļu no valsts iekšzemes kopprodukta un vairāk nekā trešdaļu darbavietu. 24. aprīlī gar Indijas un Pakistānas demarkācijas līniju Kašmirā sākās apšaudes ar strēlnieku ieročiem, kam dažas dienas vēlāk pievienojās arī artilērija. 28. aprīlī Pakistānas aizsardzības ministrs Asifs Havadža paziņoja, ka Indijas uzbrukums Pakistānai esot nenovēršams. Pastāv bažas, ka laikā, kad pārējai pasaulei citu rūpju gana, briest nopietna eskalācija starp divām kodolvalstīm Āzijas dienvidos. Sagatavoja Eduards Liniņš.

Aging-US
Inhibiting ADAM19 Reduces Gut Inflammation and Cell Aging Markers Across Species

Aging-US

Play Episode Listen Later Apr 29, 2025 4:18


BUFFALO, NY — April 29, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 3, on March 20, 2025, titled “Inhibition of the metalloprotease ADAM19 as a novel senomorphic strategy to ameliorate gut permeability and senescence markers by modulating senescence-associated secretory phenotype (SASP).” Researchers, led by first author Sudipta Bar and corresponding authors Amit Sharma and Pankaj Kapahi from the Buck Institute for Research on Aging, have found that the enzyme ADAM19 plays an important role in regulating aging in cells and inflammation in the gut. Their study shows that blocking ADAM19 reduced gut damage and inflammation in fruit flies, mice, and human cells. This discovery points to a new possible way to treat gut disorders related to aging by reducing the harmful signals from senescent (aging) cells. As individuals age, DNA damage can lead to the accumulation of senescent cells, contributing to tissue damage. These are cells that stop dividing and release harmful inflammatory substances called the senescence-associated secretory phenotype (SASP). In this study, researchers used fruit flies to search for genes involved in radiation-related gut damage. They identified a gene called meltrin, which is similar to human ADAM19. When meltrin was turned off, the flies had less gut leakage, less inflammation, and fewer signs of cellular aging. “Through an unbiased genome-wide association study (GWAS) utilizing 156 strains from the Drosophila Genetic Reference Panel (DGRP), we identified meltrin (the drosophila orthologue of mammalian ADAM19) as a potential modulator of the senescence-associated secretory phenotype (SASP).” To test if these results applied beyond flies, the team inhibited ADAM19 in mice using a drug called batimastat. Mice treated with the drug after chemotherapy exposure had stronger gut barriers and lower levels of inflammatory markers. The findings extended to human cell cultures, where ADAM19 inhibition reduced signs of cellular aging, including the expression of SASP proteins and β-galactosidase, a classic aging marker. Importantly, this approach does not kill aging cells like many 'senolytic' therapies but instead reduces the harmful substances they release, making it a potential "senomorphic" strategy. The study also showed that ADAM19 helps release certain SASP proteins by cutting them at the cell surface, suggesting a direct role in regulating inflammatory signals. Through proteomic analysis, the team identified 12 SASP proteins that were significantly reduced when ADAM19 was blocked. Many of these proteins are linked to inflammation, immune response, and tissue remodeling in diseases such as inflammatory bowel disease and Crohn's disease. This connection underlines the relevance of the findings for treating chronic gut disorders in aging populations. By targeting ADAM19, researchers may have found a new way to protect gut health and lower inflammation caused by aging cells. This study offers a promising path for creating treatments that maintain healthy tissues without having to destroy aging cells, which could benefit people with gut damage related to aging or medical treatments. DOI - https://doi.org/10.18632/aging.206224 Corresponding authors - Amit Sharma - amit.sharma@sens.org, and Pankaj Kapahi - pkapahi@buckinstitute.org Video short - https://www.youtube.com/watch?v=dRfxQ20O2fQ Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit our website at https://www.Aging-US.com​​. MEDIA@IMPACTJOURNALS.COM

Radio Marija Latvija
Sarkanie karogi un paaudžu (ne)saspēle | Mēs gribējām lidot | Daina Žurilo | Judīte Zusmane | 14.03.2025

Radio Marija Latvija

Play Episode Listen Later Apr 3, 2025 51:45


Raidījuma pirmajā daļā aplūkojam gatavojoties laulībām, kādus “sarkanos karogus” pamanot, tos neignorēt. Otrajā daļā par to, cik svarīgi vecākiem ir ļaut jauni nodobinātai ģimenei dzīvot savu dzīvi.

staYoung - Der Longevity-Podcast
Seneszente Zellen – Experte Prof. Schmitt erklärt, wie ihre Bekämpfung Sinn machen könnte

staYoung - Der Longevity-Podcast

Play Episode Listen Later Oct 25, 2024 51:38


In diesem Podcast spreche ich mit Prof. Dr. Clemens Schmitt, Professor für Hämatologie und Onkologie und leitender Forscher an der Charité Universitätsmedizin. Prof. Schmitt ist leitender Forscher am Max-Planck Delbrück-Zentrum für molekulare Medizin, dazu Direktor an der Uniklinik Linz und überhaupt international anerkannter Experte auch und besonders in Sachen zelluläre Seneszenz. Professor Clemens Schmidt erforscht mit seinem Team, wie und welche Senolytika beim Kampf gegen seneszente Zellen wirken könnten.   In dieser Folge behandeln wir unter anderem folgende Fragen: Was sind seneszente Zellen, und welche Rolle spielen sie im Alterungsprozess? Inwiefern sind seneszente Zellen verantwortlich für Alterskrankheiten wie Osteoarthritis, Fibrosen, Diabetes und neurodegenerative Erkrankungen wie Alzheimer? Wie beeinflusst der von seneszenten Zellen ausgeschüttete seneszenz-assoziierte sekretorische Phänotyp (SASP) den Alterungsprozess und die Entstehung von altersbedingten Entzündungen? Wie führt eine Chemotherapie bei jungen Menschen zu einer vermehrten Bildung von seneszenten Zellen, und welche langfristigen Auswirkungen hat dies auf das Altern? Was sind Senolytika, und wie wirken Substanzen wie Dasatinib, Quercetin und Fisetin bei der Eliminierung seneszenter Zellen? Welche ersten klinischen Erfolge wurden bei der Anwendung von Senolytika erzielt, und bei welchen Alterskrankheiten zeigen sie bereits Wirkung?   Weitere Informationen zu Prof. Schmitt findest du hier: https://www.bsio-cancerschool.de/bsio-faculty Du interessierst dich für Gesunde Langlebigkeit (Longevity) und möchtest ein Leben lang gesund und fit bleiben, dann folge mir auch auf den sozialen Kanälen bei Instagram, TikTok, Facebook oder Youtube. https://www.instagram.com/nina.ruge.official https://www.tiktok.com/@nina.ruge.official https://www.facebook.com/NinaRugeOffiziell https://www.youtube.com/channel/UCOe2d1hLARB60z2hg039l9g   Disclaimer: Ich bin keine Ärztin und meine Inhalte ersetzen keine medizinische Beratung. Bei gesundheitlichen Fragen wende dich bitte an deinen Arzt/deine Ärztin.   STY-127

Aging-US
New Model to Study Macrophage Aging Mechanisms

Aging-US

Play Episode Listen Later Oct 24, 2024 3:06


BUFFALO, NY- October 24, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science), Volume 16, Issue 19 on October 3, 2024, entitled “A new model and precious tool to study molecular mechanisms of macrophage aging.” As highlighted in the abstract, the accumulation of senescent cells, marked by a senescence-associated secretory phenotype (SASP), plays a role in chronic inflammation and age-related diseases (ARD). During aging, macrophages can develop a senescent-like phenotype with altered functions, promoting the buildup of senescent cells. In the context of aging and ARD, controlling the resolution of inflammation and preventing chronic inflammation—particularly by targeting macrophages—should be a priority. In their paper, researchers Rémy Smith, Kévin Bassand, Ashok Dussol, Christophe Piesse, Eric Duplus, and Khadija El Hadri from Sorbonne Université in Paris and Université Sorbonne Paris Nord in Bobigny, France, developed an in vitro model of murine peritoneal macrophage aging. Using this model, they demonstrated that chronic treatment with CB3, a thioredoxin-1 mimetic anti-inflammatory peptide, completely prevents the increase of p21CIP1 and allows day 14 macrophages to maintain their proliferative activity. "We describe a new model of macrophage aging with a senescence-like phenotype associated with inflammatory, metabolic and functional perturbations.” DOI - https://doi.org/10.18632/aging.206124 Corresponding authors - Eric Duplus - eric.duplus@sorbonne-universite.fr, and Khadija El Hadri - khadija.zegouagh@sorbonne-universite.fr Video short - https://www.youtube.com/watch?v=LfN78LR-CYU Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206124 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, macrophage, inflammation, senescence, thioredoxin-1 mimetic peptide About Aging-US The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population. The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.) Please visit our website at https://www.Aging-US.com​​ and connect with 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/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Aging-US
Longevity & Aging Series (S2, E2): Dr. Ming Yu and Namita Hattangady

Aging-US

Play Episode Listen Later Oct 8, 2024 63:56


In this installment of the Longevity & Aging Series, Dr. Ming Yu and Namita Hattangady from the Fred Hutchinson Cancer Center in Seattle, join host Dr. Evgeniy Galimov to discuss a research paper they co-authored that was published as the cover for Volume 16, Issue 4 of Aging (Aging-US), entitled, “Mapping the core senescence phenotype of primary human colon fibroblasts.” DOI - https://doi.org/10.18632/aging.205577 Corresponding authors - William M. Grady - wgrady@fredhutch.org, and Ming Yu - myu@fredhutch.org Video interview - https://www.youtube.com/watch?v=eqSa7My_a7w Interview transcription - https://www.aging-us.com/interviews/longevity-aging-series-s2-e2-dr-ming-yu-and-namita-hattangady Abstract Advanced age is the largest risk factor for many diseases and several types of cancer, including colorectal cancer (CRC). Senescent cells are known to accumulate with age in various tissues, where they can modulate the surrounding tissue microenvironment through their senescence associated secretory phenotype (SASP). Recently, we showed that there is an increased number of senescent cells in the colons of CRC patients and demonstrated that senescent fibroblasts and their SASP create microniches in the colon that are conducive to CRC onset and progression. However, the composition of the SASP is heterogenous and cell-specific, and the precise senescence profile of colon fibroblasts has not been well-defined. To generate a SASP atlas of human colon fibroblasts, we induced senescence in primary human colon fibroblasts using various in vitro methods and assessed the resulting transcriptome. Using RNASequencing and further validation by quantitative RT-PCR and Luminex assays, we define and validate a ‘core senescent profile' that might play a significant role in shaping the colon microenvironment. We also performed KEGG analysis and GO analyses to identify key pathways and biological processes that are differentially regulated in colon fibroblast senescence. These studies provide insights into potential driver proteins involved in senescence-associated diseases, like CRC, which may lead to therapies to improve overall health in the elderly and to prevent CRC. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205577 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, senescence, senescence associated secretory phenotype, SASP, colorectal cancer, cancer About Aging-US The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population. The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.) Please visit our website at https://www.Aging-US.com​​ and connect with 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/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Divas puslodes
Ko paredzēs Ukrainas "Uzvaras plāns"? Pieaug saspīlējums starp Izraēlu un "Hizbullāh"

Divas puslodes

Play Episode Listen Later Sep 25, 2024 53:59


Ņujorkā ir pulcējušies pasaules valstu līderi, lai tiktos ANO Ģenerālajā asamblejā. Protams, ne no visām valstīm ir ieradušies prezidenti. Vladimirs Putins tur nevar doties, neriskējot ar savu brīvību. Tajā pašā laikā Ukrainas prezidenta Zelenska braucienam ir pievērsta īpaša uzmanība. Viņš grasās prezentēt gan esošajam, gan iespējamajiem ASV prezidentiem savu "miera plānu".  Skaidrs, ka šajā asamblejā galvenā uzmanība veltīta diviem lielajiem kariem, gan Krievijas agresijai, gan tam, kas notiek Tuvajos Austrumos. Pēc intensīvajiem gaisa triecieniem Libānā, kas turpinās un kuros bojā gājuši vairāk nekā 500 cilvēku, arvien lielāka ir iespējamība, ka karš izplatīsies plašākā reģionā.  Aktualitātes analizē Latvijas Radio ziņu dienesta žurnālists Uldis Ķezberis, Austrumeiropas politikas pētījumu centra pētnieks Armands Astukevičs un Nacionālo bruņoto spēku pārstāvis, majors Jānis Slaidiņš. Pieaug saspīlējums starp Izraēlu un grupējumu „Hizbullāh” Vismaz pustūkstoša bojāgājušo, no kuriem 50 ir bērni, un tūkstošiem ievainoto Libānā, - tā ir statistika kopš pirmdienas, kad Izraēla uzsāka ļoti intensīvus uzlidojumus, vērstus pret grupējumu „Hizbullāh”. Kā pagājušajā nedēļā paziņoja Izraēlas aizsardzības ministrs, karš ir iegājis jaunā stadijā, un tagad fokuss vairāk būšot pievērsts ziemeļiem. Jauno stadiju iezīmēja peidžeru uzspridzināšana, kas nogalināja vairākus desmitus, bet savainoja tūkstošiem kaujinieku. Līdz ar šīsnedēļas uzlidojumiem Libānas slimnīcas ir pārpildītas, un tas Libānas medicīnai ir milzīgs izaicinājums. Taču runa nav tikai par veselības aprūpes sistēmu. Tūkstošiem ģimeņu ir devušās bēgļu gaitās, bēgot no Izraēlas apšaudītajiem rajoniem. Valstī, kas jau līdz šim ir cīnījusies ar pamatīgu ekonomisko krīzi, tas ir liels izaicinājums. Kā no Beirutas ziņo žurnālisti, Libānā aug gan dusmas, gan bailes par tālākajiem notikumiem. Šodien, 25. septembrī, ANO sasaukta drošības padomes sēde, lai spriestu par notiekošo. „Libāna ir bezdibeņa kraujas malā. Libānas tauta, Izraēlas tauta, visi pasaules iedzīvotāji nedrīkst pieļaut, ka Libāna kļūst par otro Gazu,” tā izteicies ANO ģenerālsekretārs Antonio Gutērešs. Arī valstu vadītāji, kas pulcējušies uz ANO Ģenerālo asambleju, aicina darīt visu iespējamo, lai apturētu pilna mēroga karu Tuvajos Austrumos. Daudzi gan uzskata, ka tikai ASV var ietekmēt Izraēlu. Pentagons pirmdien ziņoja, ka Amerikas Savienotās valstis, reaģējot uz pieaugošajiem draudiem, nosūtīs uz Tuvajiem Austrumiem papildus savus karavīrus, tomēr to skaits nebūšot liels.  Noslēpumainais Ukrainas „Uzvaras plāns” „Mēs nekad neesam atbalstījuši Krievijas agresiju pret Ukrainas teritoriju,” tā, ierodaties uz ANO Ģenerālo asambleju Ņujorkā, sarunā ar žurnālistiem apgalvoja Irānas nesen ievēlētais prezidents Masuds Pezeškiāns. Kopš viņš esot prezidents, uz Krieviju neesot nosūtītas Irānas raķetes. Tāpēc viņš vēloties sarunas ar Rietumvalstu vadītājiem, kā izbeigt karu Ukrainā. Lai gan Irānas vadības teiktajam daudzi netic, tomēr viņa teiktais par Krievijas agresiju un aicinājums uz sarunām ir interesants. Karš Ukrainā ir otrs lielais izaicinājums, kam Ņujorkā pievērsta īpaša uzmanība. To paspilgtina Ukrainas prezidenta Volodimira Zelenska vizīte, kas ir plašāka nekā tikai uzstāšanās ANO mītnē. Viņš ASV ieradās jau 22. septembrī. Zelenskim ir ļoti saspringts darba grafiks, un kulminācija ir ne tik daudz uzstāšanās asamblejā, cik viņa tikšanās ar ASV prezidentu Džo Baidenu un abiem prezidenta amata kandidātiem – gan Kamalu Harisu, gan Donaldu Trampu. Pēdējais jau ir paspējis pavīpsnāt par Zelenska ierašanos, nosaucot viņu par labāko pārdevēju vēsturē, tomēr tikšanās, jādomā, notiks. Galvenā uzmanība ir pievērsta Ukrainas prezidenta teiktajam par viņa atvesto miera plānu. Medijos nerimst spekulācijas, ko šis plāns paredz. Līdz šim izskanējusī informācija ir ļoti pretrunīga, un ņemot vērā to, ka tas drīz tiks publiskots, daudzi eksperti negaida tur ieraudzīt ko nezināmu vai neparastu. Iespējams, ka publiskajā telpā būs redzams kas cits nekā tas, ko patiešām Ukraina ir iecerējusi. Jebkurā gadījumā ziņas, kas pienāk no Kijivas, ir uzmanību raisošas. No vienas puses, Ukrainas armija joprojām izmisīgi cenšas aizstāvēt savas teritorijas, vietumis piekāpjoties ienaidnieka pārspēka priekšā. No otras puses, tā cenšas pastiprināt ofensīvu Kurskas apgabalā Krievijas teritorijā. No trešās, tiek izteikti neslēpti mājieni, ka tuvākajos mēnešos ir gaidāmi notikumi, kas varētu būtiski ietekmēt kara gaitu. Par kādiem notikumiem ir runa, var tikai minēt. Arī Zelenskis intervijā šonedēļ izteicās, ka kara noslēgums varētu būt tuvāk nekā daudziem tas šķiet.  Eiropas Parlamenta granta projekta „Jaunā Eiropas nākotne” programma.* * Šī publikācija atspoguļo tikai materiāla veidošanā iesaistīto pušu viedokli. Eiropas Parlaments nav atbildīgs par tajā ietvertās informācijas jebkādu izmantošanu.

SaaS Acquisition Stories
How to Build a Profitable SaaS in 6 Months and Sell it in 5 Days

SaaS Acquisition Stories

Play Episode Listen Later Sep 25, 2024 20:49


Software businesses can be immensely profitable in very little time. But they can also die just as quickly. Software engineer Mark Jivko built Go index me!, a tool that speeds up Google page indexing, in six months for a bit of extra cash. He grew it to over 150 regular customers and thousands of dollars in sales in under a year. But Mark knew building an app that only relied on the Google APIs was playing with fire. It could all be demolished with a keystroke during a system update. He wanted to sell while he was ahead so that he could move onto another project he was more passionate about. Mark had previously sold a business on Acquire.com and knew he'd find the buyer he was looking for there. He sold Go index me! in one week under the tutelage of his buyer, an eight-time serial startup acquirer who DM'd him almost immediately. Now Mark is gearing up for a new project to help founders using social media for product distribution to avoid platform addiction. Tune in to this SASP with Mark and Andrew as they discuss: Mark's trick to do escrows faster The questions you should never answer from buyers before going under LOI Why Mark knew he was going to sell his tool from the beginning How Mark plans to help founders who use social media reduce their addictions to the platforms And read our writeup of Mark's story here. Mark is just getting started and you can follow him below: LinkedIn Twitter

Aging-US
Links Between Exercise, Senescence, and Lung Health

Aging-US

Play Episode Listen Later Jul 18, 2024 5:27


Over the human lifespan, our cells encounter numerous stressors that can trigger an intrinsic defense mechanism called cellular senescence. Cellular senescence is characterized by irreversible growth arrest and can act as a safeguard against cancer. However, when senescent cells accumulate in various tissues as we age, it can contribute to tissue degeneration and chronic diseases. The senescence-associated secretory phenotype (SASP), a hallmark of senescent cells, plays a critical role by secreting inflammatory factors, proteases, and growth factors, disrupting tissue balance and fueling pathological conditions. Consequently, selectively eliminating senescent cells has emerged as a promising therapeutic strategy, potentially restoring tissue function and mitigating age-related disorders. Full blog - https://aging-us.org/2024/07/links-between-exercise-senescence-and-lung-health/ Research Paper DOI - https://doi.org/10.18632/aging.205976 Corresponding author - Masataka Sugimoto - msugimot@tmig.or.jp Video short - https://www.youtube.com/watch?v=Bzgb2PEiV9c Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205976 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, senescence, exercise, PEDF, myokine, COPD About Aging-US The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population. The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.) Please visit our website at https://www.Aging-US.com​​ and connect with 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/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Aging-US
Modulating Lung Fibroblast Activation via Senolysis of Senescent Human Alveolar Epithelial Cells

Aging-US

Play Episode Listen Later Jul 17, 2024 3:46


BUFFALO, NY- July 17, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 13, entitled, “Modulating in vitro lung fibroblast activation via senolysis of senescent human alveolar epithelial cells.” Idiopathic pulmonary fibrosis (IPF) is an age-related disease with poor prognosis and limited therapeutic options. Activation of lung fibroblasts and differentiation to myofibroblasts are the principal effectors of disease pathology, but damage and senescence of alveolar epithelial cells, specifically type II (ATII) cells, has recently been identified as a potential trigger event for the progressive disease cycle. Targeting ATII senescence and the senescence-associated secretory phenotype (SASP) is an attractive therapeutic strategy; however, translatable primary human cell models that enable mechanistic studies and drug development are lacking. In this new study, researchers Joseph S. Spina, Tracy L. Carr, Lucy A. Phillips, Heather L. Knight, Nancy E. Crosbie, Sarah M. Lloyd, Manisha A. Jhala, Tony J. Lam, Jozsef Karman, Meghan E. Clements, Tovah A. Day, Justin D. Crane, and William J. Housley from AbbVie Bioresearch Center and Northeastern University describe a novel system of conditioned medium (CM) transfer from bleomycin-induced senescent primary alveolar epithelial cells (AEC) onto normal human lung fibroblasts (NHLF) that demonstrates an enhanced fibrotic transcriptional and secretory phenotype compared to non-senescent AEC CM treatment or direct bleomycin damage of the NHLFs. “In the current study, we confirm the presence of senescent cell populations within the human IPF lung, as well as assess primary cell reagents for sensitivity to senescent cell targeting therapies.” In this system, the bleomycin-treated AECs exhibited classical hallmarks of cellular senescence, including SASP and a gene expression profile that resembles aberrant epithelial cells of the IPF lung. Fibroblast activation by CM transfer was attenuated by pre-treatment of senescent AECs with the senolytic Navitoclax and AD80, but not with the standard of care agent Nintedanib or senomorphic JAK-targeting drugs (e.g., ABT-317, ruxolitinib). This model provided a relevant human system for profiling novel senescence-targeting therapeutics for IPF drug development. “Taken together, the model described herein provides a physiologically relevant, primary human cell system to study the effects of alveolar epithelial cell senescence on lung fibroblasts in the context of chronic fibrotic lung disease.” DOI - https://doi.org/10.18632/aging.205994 Corresponding author - Tovah A. Day - t.day@northeastern.edu Video short - https://www.youtube.com/watch?v=rpmo2PlGDKc Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205994 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts About Aging-US The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population. The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.) Please visit our website at https://www.Aging-US.com​​ and connect with 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/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

SaaS Acquisition Stories
Startup Acquisition Stories With Eric Pacifici of SMB Law Group

SaaS Acquisition Stories

Play Episode Listen Later Jun 26, 2024 17:46


What are the three biggest mistakes SME buyers make when choosing an M&A lawyer? M&A professional Eric Pacifici says new buyers often pick lawyers who: Aren't entrepreneurial Bill hourly rather than flat rate Don't have M&A experience After years of cementing billion-dollar deals at Kirkland & Ellis (the largest firm in the world by revenue), Eric decided he liked smaller deals better. He decided to jump into the world of small business acquisitions. Eric is well-known on the internet for his Twitter account (@smb_attorney) and for coining the term “silver tsunami” i.e.the coming wealth transfer between baby boomers and their offspring. He realized a few years ago that many of these boomers' small businesses would be put up for sale in the coming years. To confront this coming wave of small acquisitions, Eric teamed up with a team of fellow lawyers from large firms with a passion for smaller deals to create SMB Law Group.  SMB Law today specializes specifically in entrepreneurship-by-acquisition deals. Those are deals where aspiring entrepreneurs get a running start by purchasing a fully functioning business. Business has been heating up. The firm did $950 million in closings just last year. Eric and SMB Law are fast becoming the go-to lawyers for people trying to buy small and medium-sized businesses in the US. This week, Eric hopped on the SASP with Andrew Gazdecki to discuss: Where Eric thinks most deals go wrong Why you need a good lawyer when buying a business for $1 million+ Andrew's lawyer billing horror story Eric is just getting started and you can contact and follow him below: Eric@smblaw.group @smb_attorney (Twitter) LinkedIn

SaaS Acquisition Stories
Startup Acquisition Stories With Hussein Reda, Founder of Propty

SaaS Acquisition Stories

Play Episode Listen Later Jun 18, 2024 25:19


Here's a fun stat for you, the homeowner association (HOA) industry in the US alone was worth $38.8 billion in 2023. Hussein Reda tapped into some of that value during the Covid lockdowns when he created his startup, Propty, to help HOA meetings run meetings and vote remotely. Pre-Covid, Hussein had just purchased his first property in an apartment building. He learned a lot of maintenance was done through HOAS, aka, groups that manage properties in specific buildings/neighborhoods. Once Covid hit, everyone was trapped inside and began attending HOA meetings since now they had lots of time to think about their homes. Hussein saw an opportunity, created Propty, and used his HOA as his first free test customer. Propty went through two years of ups and downs including embarrassing meetings with 500+ members where not everyone could connect. Everything was made more complicated by the fact that HOA meetings only happened once a year. However, after persistent effort, Hussein secured his first paying customers by mid-2023. Finally, Hussein sold Propty on Acquire.com in 2024 when he realized he didn't know how to scale any further. Now he's working on a project with blockchain technology to facilitate payments for underbanked countries. Tune into this week's SASP as Andrew and Husseing discuss: The hidden gem of the HOA industry Why boring businesses are the best money-makers Why Hussein thinks Acquire.com sales beat other online sales forums Hussien is just getting started and you can follow his journey below: https://www.linkedin.com/in/hussein-reda/ ▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬ Be sure to subscribe to see the newest acquisition stories every Tuesday and gain the knowledge to buy or sell your own online business → here Want more stories? Access the past 50+ acquisition stories here → here Thinking about selling your own startup? The number one question is always 'how much can I sell for' and we've got the answers in our biannual valuation multiples reports here → here Thinking about buying a startup? Sign up for a free buyer account and browse all the live listings. Upgrade only when you find the right one that fits your acquisition criteria to engage. Get Started → here ▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬ Follow the Guest: Hussein Reda   ► https://www.linkedin.com/in/hussein-reda/⁠ Follow the Host: Andrew Gazdecki -  ► https://twitter.com/agazdecki​ ► https://www.linkedin.com/in/agazdecki/​ ► https://acquire.com Follow Acquire.com - ► https://twitter.com/acquiredotcom ► https://www.linkedin.com/company/acquiredotcom ► https://www.tiktok.com/@acquiredotcom ▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬ About Acquire.com: Acquire.com is the largest and most active acquisition marketplace for buying and selling online businesses. Acquire.com is the highest rated platform for both ease and quickness to match buyers and sellers.  We cater to all types of online, revenue-generating businesses while producing the highest success rates for SaaS and eCommerce/DTC businesses in the M&A industry. Join over 350,000 entrepreneurs making life-changing connections and deals everyday.

Aging-US
Modulation of Senescence Features Using Weo Electrolyzed Water

Aging-US

Play Episode Listen Later May 22, 2024 4:22


BUFFALO, NY- May 22, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 9, entitled, “Cell type-dependent modulation of senescence features using Weo electrolyzed water.” Electrolyzed-reduced water has powerful antioxidant properties with constituents that scavenge reactive oxygen species (ROS), which are known to be produced by several intrinsic and extrinsic processes. When there is an imbalance between ROS production and antioxidant defenses, oxidative stress occurs. Persistent oxidative stress leads to cellular senescence, an important hallmark of aging, and is involved in several age-related conditions and illnesses. In this new study, researchers Brenda L. Court-Vazquez, Shirley A. Arroyo-Vizcarrondo, Jonathan A. Poli, Lara Nyman, Kelly Halderman, Anthony Ginter, and Pierre-Yves Desprez from Weo LLC and California Pacific Medical Center investigated whether Weo electrolyzed water (WEW) could modulate the phenotype of senescent cells. “The focus of this study was to utilize two different cell types, human normal fibroblasts and human breast cancer cells, to investigate the impact of Weo electrolyzed water (WEW) on markers of cellular senescence, inflammation, and stress response genes.” The researchers compared normal human lung fibroblasts (BJ) and breast cancer cells (T47D) treated with hydrogen peroxide (H2O2) to induce senescence. They assessed the molecular impact of WEW on markers of cellular senescence, senescence-associated secretory phenotype (SASP) factors, and stress response genes. Treatment with WEW modulated markers of cellular senescence, such as the senescence-associated β-galactosidase (SA-β-gal) activity, EdU incorporation and p21 expression, similarly in both cell types. However, WEW modulated the expression of SASP factors and stress response genes in a cell type-dependent and opposite fashion, significantly decreasing them in BJ cells, while stimulating their expression in T47D cells. Reduction in the expression of SASP factors and stress-related genes in BJ cells suggests that WEW acts as a protective factor, thereby reducing oxidative stress in normal cells, while making cancer cells more sensitive to the effects of cellular stress, thus increasing their elimination and consequently reducing their deleterious effects. “In conclusion, we have shown here that the new technology developed by Weo, WEW, could attenuate the overall process of cellular senescence in both normal BJ fibroblasts and cancer T47D cells.” DOI - https://doi.org/10.18632/aging.205789 Corresponding authors - Brenda L. Court-Vazquez - bco@we-o.com, and Pierre-Yves Desprez - pydesprez@cpmcri.org Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, cellular senescence, senescence-associated secretory phenotype, oxidative stress, lung fibroblasts, breast cancer cells, senomorphic About Aging-US Aging publishes research papers in all fields of aging research, including but not limited to aging processes (from yeast to mammals), cellular senescence, age-related diseases (such as cancer and Alzheimer's disease) and their prevention and treatment, anti-aging strategies and drug development, and, importantly, the role of signal transduction pathways in aging (such as mTOR) and potential approaches to modulate these signaling pathways to extend lifespan. Please visit our website at https://www.Aging-US.com​​ and connect with 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/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

SaaS Acquisition Stories
Startup Acquisition Stories Podcast With Doug Mitchell of Scale LLP

SaaS Acquisition Stories

Play Episode Listen Later May 20, 2024 14:40


Acquisition lawyer at Scale LLP, Doug Mitchell, recalls one of the closest calls he's ever encountered while advising a sale. For this episode of SASP, Doug sat down with Andrew Gazdecki to discuss: What kinds of deals he does What lawyers normally manage in SME deals How much he charges for his retainer And what Doug does in his free time. ▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬ Be sure to subscribe to see the newest acquisition stories every Tuesday and gain the knowledge to buy or sell your own online business → https://youtube.com/@acquiredotcom?sub_confirmation=1 Want more stories? Access the past 50+ acquisition stories here → https://blog.acquire.com/tag/startup-acquisition-stories-podcast/ Thinking about selling your own startup? The number one question is always 'how much can I sell for' and we've got the answers in our biannual valuation multiples reports here → https://blog.acquire.com/tag/acquire-coms-acquisition-multiples-report/ Thinking about buying a startup? Sign up for a free buyer account and browse all the live listings. Upgrade only when you find the right one that fits your acquisition criteria to engage. Get Started → https://acquire.com/buyers/ ▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬ Follow the Host: Andrew Gazdecki https://twitter.com/agazdecki https://www.linkedin.com/in/agazdecki/ https://acquire.com Follow Acquire.com - https://twitter.com/acquiredotcom https://www.linkedin.com/company/acquiredotcom https://www.tiktok.com/@acquiredotcom ▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬ About Acquire.com: Acquire.com is the largest and most active acquisition marketplace for buying and selling online businesses. Acquire.com is the highest rated platform for both ease and quickness to match buyers and sellers. We cater to all types of online, revenue-generating businesses while producing the highest success rates for SaaS and eCommerce/DTC businesses in the M&A industry. Join over 500,000 entrepreneurs making life-changing connections and deals everyday.

SaaS Acquisition Stories
Startup Acquisitions Stories Podcast With Nour Shaban, Founder of a SaaS Acquired for 7-Figures

SaaS Acquisition Stories

Play Episode Listen Later Apr 24, 2024 18:12


Lebanese founder, Nour Shaban just sold his SaaS business on Acquire.com for a life-changing sum. While he can't reveal too many details due to his non-disclosure agreement (NDA), he agreed to hop on the SASP podcast to talk about his experience building and selling his business. Listen to Nour's chat with Andrew as they discuss: The benefits of the Guided by Acquire process that can't be found anywhere else How the Acquire.com experience compares to the old MicroAcquire experience Advice to other entrepreneurs trying to create a 7-figure exit ▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬ Be sure to subscribe to see the newest acquisition stories every Tuesday and gain the knowledge to buy or sell your own online business → https://youtube.com/@acquiredotcom?sub_confirmation=1 Want more stories? Access the past 50+ acquisition stories here → https://blog.acquire.com/tag/startup-acquisition-stories-podcast/ Thinking about selling your own startup? The number one question is always 'how much can I sell for' and we've got the answers in our biannual valuation multiples reports here → https://blog.acquire.com/tag/acquire-coms-acquisition-multiples-report/ Thinking about buying a startup? Sign up for a free buyer account and browse all the live listings. Upgrade only when you find the right one that fits your acquisition criteria to engage. Get Started → https://acquire.com/buyers/ ▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬ Follow the Host: Andrew Gazdecki https://twitter.com/agazdecki https://www.linkedin.com/in/agazdecki/ https://acquire.com Follow Acquire.com - https://twitter.com/acquiredotcom https://www.linkedin.com/company/acquiredotcom https://www.tiktok.com/@acquiredotcom ▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬ About Acquire.com: Acquire.com is the largest and most active acquisition marketplace for buying and selling online businesses. Acquire.com is the highest rated platform for both ease and quickness to match buyers and sellers. We cater to all types of online, revenue-generating businesses while producing the highest success rates for SaaS and eCommerce/DTC businesses in the M&A industry. Join over 350,000 entrepreneurs making life-changing connections and deals everyday.

Aging-US
Mapping the Core Senescence Phenotype of Human Colon Fibroblasts

Aging-US

Play Episode Listen Later Feb 29, 2024 3:30


BUFFALO, NY- February 29, 2024 – A new #research paper was #published on the #cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 4, entitled, “Mapping the core senescence phenotype of primary human colon fibroblasts.” Advanced age is the largest risk factor for many diseases and several types of cancer, including colorectal cancer (CRC). Senescent cells are known to accumulate with age in various tissues, where they can modulate the surrounding tissue microenvironment through their senescence associated secretory phenotype (SASP). Recently, researchers showed that there is an increased number of senescent cells in the colons of CRC patients and demonstrated that senescent fibroblasts and their SASP create microniches in the colon that are conducive to CRC onset and progression. However, the composition of the SASP is heterogenous and cell-specific, and the precise senescence profile of colon fibroblasts has not been well-defined. In this new study, to generate a SASP atlas of human colon fibroblasts, researchers Namita Ganesh Hattangady, Kelly Carter, Brett Maroni-Rana, Ting Wang, Jessica Lee Ayers, Ming Yu, and William M. Grady from Fred Hutchinson Cancer Center and the University of Washington School of Medicine induced senescence in primary human colon fibroblasts using various in vitro methods and assessed the resulting transcriptome. “[...] we utilized various relevant stressors to induce senescence in primary cultures of colon fibroblasts and perform RNA sequencing (RNASeq) to define an atlas of stressor-specific senescent profiles and a core senescent profile that is commonly regulated by all senescence inducers.” Using RNA Sequencing and further validation by quantitative RT-PCR and Luminex assays, the team define and validate a ‘core senescent profile' that might play a significant role in shaping the colon microenvironment. They also performed KEGG analysis and GO analyses to identify key pathways and biological processes that are differentially regulated in colon fibroblast senescence. These studies provide insights into potential driver proteins involved in senescence-associated diseases, like CRC, which may lead to therapies to improve overall health in the elderly and to prevent CRC. “Further studies will be needed to address the limitations of our study and to translate our understanding of the SASP and disease into clinical care.” DOI - https://doi.org/10.18632/aging.205577 Corresponding authors - William M. Grady - wgrady@fredhutch.org, and Ming Yu - myu@fredhutch.org Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205577 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, senescence, senescence associated secretory phenotype, SASP, colorectal cancer, cancer 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: 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/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Aging-US
Unique Pathogenic Mechanism of SARS-CoV-2 Omicron Variant: Induction of Cellular Senescence

Aging-US

Play Episode Listen Later Dec 15, 2023 4:17


BUFFALO, NY- December 15, 2023 – A new #researchpaper was #published on the #cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 23, entitled, “Uncovering a unique pathogenic mechanism of SARS-CoV-2 omicron variant: selective induction of cellular senescence.” SARS-CoV-2 variants are constantly emerging with a variety of changes in the conformation of the spike protein, resulting in alterations of virus entry mechanisms. Solely omicron variants use the endosomal clathrin-mediated entry. In this new study, researchers Franziska Hornung, Nilay Köse-Vogel, Claude Jourdan Le Saux, Antje Häder, Lea Herrmann, Luise Schulz, Lukáš Radosa, Thurid Lauf, Tim Sandhaus, Patrick Samson, Torsten Doenst, Daniel Wittschieber, Gita Mall, Bettina Löffler, and Stefanie Deinhardt-Emmer from Jena University, Leibniz Centre for Photonics in Infection Research (LPI), University of California San Francisco, Klinik für Herz- und Thoraxchirurgie, and University Hospital Bonn investigated the influence of defined altered spike formations to study their impact on premature cellular senescence. “In our study, in vitro infections of SARS-CoV-2 variants delta (B.1.617.2) and omicron (B.1.1.529) were analyzed by using human primary small alveolar epithelial cells and human ex vivo lung slices. We confirmed cellular senescence in human lungs of COVID-19 patients. Hence, global gene expression patterns of infected human primary alveolar epithelial cells were identified via mRNA sequencing.” Solely omicron variants of SARS-CoV-2 influenced the expression of cell cycle genes, highlighted by an increased p21 expression in human primary lung cells and human ex vivo lungs. Additionally, an upregulated senescence-associated secretory phenotype (SASP) was detected. Transcriptomic data indicate an increased gene expression of p16, and p38 in omicron-infected lung cells. Significant changes due to different SARS-CoV-2 infections in human primary alveolar epithelial cells with an overall impact on premature aging could be identified. A substantially different cellular response with an upregulation of cell cycle, inflammation- and integrin-associated pathways in omicron infected cells indicates premature cellular senescence. “This difference may be attributed to the distinct endocytic cell entry and intracellular pathways of the omicron variant when compared to the delta variant. The induction of cellular senescence in lung tissue following acute SARS-CoV-2 infection could potentially contribute to the reported cytokine storm and the development of long-COVID.” DOI - https://doi.org/10.18632/aging.205297 Corresponding author - Stefanie Deinhardt-Emmer - stefanie.deinhardt-emmer@med.uni-jena.de Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, SARS-CoV-2, variant of concern, cellular senescence, lung airway cells 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/ 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

Kultūras Rondo
Māksliniekam Ansim Cīrulim veltītā uzvedumā saspēlēsies Vilis Daudziņš un Jānis Šipkēvics

Kultūras Rondo

Play Episode Listen Later Nov 2, 2023 9:54


Šogad aprit 140 gadu, kopš dzimis viens no daudzpusīgākajiem latviešu “zelta paaudzes” māksliniekiem – gleznotājs, grafiķis, keramiķis, interjera dizainers un aizrautīgs “latviskā koda” meklētājs mākslā Ansis Cīrulis. Viņam veltīts koncertuzvedums "Ansis Cīrulis. Ģēnijs. Latvietis." nedēļas nogalē izskanēs Dzintaru koncertzālē. To veido spožs mākslinieku ansamblis – diriģents Sigvards Kļava un Latvijas Radio kora solisti, dramaturģe Nora Ikstena un māksliniece Anna Heinrihsone. Intriģējošā divu Cīruļu duetā uz skatuves saspēlēsies Vilis Daudziņš un Jānis Šipkēvics. Dzintaru koncertzāles izvēle uzvedumam par Ansi Cīruli nav nejauša: Cīrulis ir dzimis jūrmalnieks, un mūža nogalē, 20.gadsimta 30.gados, viņš tolaik jaunajai kultūrvietai radīja sienas gleznojumus, kas joprojām apskatāmi koncertzāles foajē. Pianista Riharda Plešanova izspēlētās Cīruļa laikabiedra, komponista Jēkaba Graubiņa miniatūras iedod kamertoni visam iestudējumam: skaņu ainavas mijas ar poētisku Anša Cīruļa dzīvesstāstu, ko izspēlē divi Cīruļi – praktiskais un racionālais Viļa Daudziņa Cīrulis un dvēseliskais sapņotājs – “cīrulītis mazputniņš” – ko izdzied Jānis Šipkēvics jeb Shipsea. Skaņu ietvaru uzvedumam radījis Latvijas Radio kora mākslinieciskais vadītājs Sigvards Kļava. Diriģents atzīst, ka atrast atbilstošu skanējumu Anša Cīruļa mākslinieciskajam rokrakstam un dvēseles izjūtai nemaz nav bijis viegli. Ansim Cīrulim veltītais iestudējums tapis Sigvarda Kļavas, rakstnieces Noras Ikstenas un mākslinieces Annas Heinrihsones ciešā radošā partnerībā, kas jau pārbaudīta, kopīgi veidojot jauno, bet vēl neapskatāmo Rakstniecības un mūzikas muzeja ekspozīciju. Šajā uzvedumā par atspēriena punktu Annai Heinrihsonei kļuvis Cīruļa alfabēts, kas šodien atdzimis par latviskā burtveidola stila ikonu. Dzimis 19.gadsimta 80.gados namdara ģimenē, Ansis Cīrulis sākumā mācījās par mūrnieku un amatnieku, pamazām izkopa zīmēšanas talantu un sešas ziemas pavadīja mācībās Parīzē. Aktierim Vilim Daudziņam šajā iestudējumā ir ilgi gaidīts un reizē ļoti sarežģīts uzdevums: viņš uz skatuves ne vien stāsta Anša Cīruļa dzīvi, bet vienlaikus arī zīmē un glezno. Daudziņš savulaik beidzis Rīgas Lietišķās mākslas vidusskolu kā metālmākslinieks. Līdzīgi kā Annai Heinrihsonei, arī Vilim Daudziņam skolas gados Anša Cīruļa un laikabiedru ornamentālā māksla nebija tuva. Interesēja zviedru dizaina askētisms, konstruktīvas formas. Ornamentu patika atnākusi pavisam nesen. Pirms un pēc koncerta apmeklētāji varēs apskatīt arī nelielu Anša Cīruļa darbu izstādi – uz Dzintaru koncertzāli būs atceļojis gan Rīgas pils Sūtņu zāles krēsls un vairākas zīmotnes, Cīruļa alfabēta klišeja un caur lupu pētāmas pilsētu ģerboņu un naudaszīmes skices. Nākotnē iecerēts koncertzāles telpās atvēlēt vietu pastāvīgai interaktīvai pieturvietai par Ansi Cīruli. Ja vēlaties vēl ko uzzināt par mākslinieku Ansim Cīrulim veltītā iestudējuma tapšanu, Latvijas Radio 3 piedāvā sarunu arī ar uzveduma libreta autori, rakstnieci Noru Ikstenu.

Authentic Biochemistry
BioMedical PortraitIIIC13c. Leucocyte and lymphocyte mediated SASP involve a corruption in robust novel immune responses while enhancing chronic autoimmune inflammation in the obese and elderly.DJGPhD

Authentic Biochemistry

Play Episode Listen Later Oct 2, 2023 29:49


References Curr Opin Pharmacol. 2021 Apr; 57: 107–116 --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

Aging-US
DNA Damage-induced Senescence Model in Osteoarthritic Chondrocytes

Aging-US

Play Episode Listen Later Sep 20, 2023 3:34


BUFFALO, NY- September 20, 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 17, entitled, “Development of a DNA damage-induced senescence model in osteoarthritic chondrocytes.” Senescent cells (SnCs) have been described to accumulate in osteoarthritis (OA) joint tissues in response to injury, thereby participating in OA development and progression. However, clinical therapeutic approaches targeting SnCs using senolysis, although promising in preclinical OA models, have not yet proven their efficacy in patients with knee OA. This pitfall may be due to the lack of understanding of the mechanisms underlying chondrocyte senescence. In their new study, researchers Mélina Georget, Anaïs Defois, Romain Guiho, Nina Bon, Sophie Allain, Cécile Boyer, Boris Halgand, Denis Waast, Gaël Grimandi, Alban Fouasson-Chailloux, Jérôme Guicheux, and Claire Vinatier from Nantes Université aimed to generate models of chondrocyte senescence. “In this context, our study aims to develop in vitro models of chondrocyte senescence by investigating the ability of etoposide and IL-1β treatments to produce a reliable chondrocyte senescent model.” This study used etoposide, to induce DNA damage-related senescence or chronic exposure to IL-1β to entail inflammation-related senescence in human OA chondrocytes. Several hallmarks of cellular senescence, such as cell cycle arrest, expression of cyclin-dependent kinase inhibitors, DNA damages, and senescence-associated secretory profile were evaluated. Chronic exposure to IL-1β induces only partial expression of senescence markers and does not allow us to conclude on its ability to induce senescence in chondrocytes. On the other hand, etoposide treatment reliably induces DNA damage-related senescence in human articular chondrocytes evidenced by loss of proliferative capacity, DNA damage accumulation, and expression of some SASP components. “Etoposide-induced senescence model may help investigate the initiation of cellular senescence in chondrocytes, and provide a useful model to develop therapeutic approaches to target senescence in OA.” DOI - https://doi.org/10.18632/aging.204881 Corresponding author - Claire Vinatier - claire.vinatier@univ-nantes.fr Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204881 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, senescence, osteoarthritis, etoposide, chondrocytes 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/ 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 Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Aging-US
Human Senescent Fibroblasts Cause Lung Fibrosis in Mice

Aging-US

Play Episode Listen Later Jul 31, 2023 4:17


A new research paper was published on the cover of Aging (Aging-US) Volume 15, Issue 14, entitled, “Human senescent fibroblasts trigger progressive lung fibrosis in mice.” Cell senescence has recently emerged as a potentially relevant pathogenic mechanism in fibrosing interstitial lung diseases (f-ILDs), particularly in idiopathic pulmonary fibrosis. In a new study, researchers Fernanda Hernandez-Gonzalez, Neus Prats, Valentina Ramponi, José Alberto López-Domínguez, Kathleen Meyer, Mònica Aguilera, María Isabel Muñoz Martín, Daniel Martínez, Alvar Agusti, Rosa Faner, Jacobo Sellarés, Federico Pietrocola, and Manuel Serrano from Hospital Clinic Barcelona, The Barcelona Institute of Science and Technology (BIST), Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University of Barcelona, Karolinska Institute, Catalan Institution for Research and Advanced Studies (ICREA), and Altos Labs hypothesized that senescent human fibroblasts may suffice to trigger a progressive fibrogenic reaction in the lung. “Here we: (1) explored this hypothesis in vivo; (2) investigated the potential underlying biological mechanisms in vitro; and (3) studied the effects of one experimental senolytic compound (navitoclax) and two anti-fibrotic drugs currently used in the treatment of IPF in humans (nintedanib and pirfenidone), both in vivo and in vitro.” To address this, senescent human lung fibroblasts, or their secretome (SASP), were instilled into the lungs of immunodeficient mice. The researchers found that human senescent fibroblasts engraft in the lungs of immunodeficient mice and trigger progressive lung fibrosis associated to increasing levels of mouse senescent cells, whereas non-senescent fibroblasts do not trigger fibrosis. They also found that the SASP of human senescent fibroblasts is pro-senescence and pro-fibrotic both in vitro when added to mouse recipient cells and in vivo when delivered into the lungs of mice, whereas the conditioned medium (CM) from non-senescent fibroblasts lacks these activities. Finally, navitoclax, nintedanib and pirfenidone were found to ameliorate lung fibrosis induced by senescent human fibroblasts in mice, while only navitoclax displayed senolytic activity. “We conclude that human senescent fibroblasts, through their bioactive secretome, trigger a progressive fibrogenic reaction in the lungs of immunodeficient mice that includes the induction of paracrine senescence in the cells of the host, supporting the concept that senescent cells actively contribute to disease progression in patients with f-ILDs.” DOI - https://doi.org/10.18632/aging.204825 Corresponding authors - Manuel Serrano - mserrano@altoslabs.com, and Federico Pietrocola - federico.pietrocola@ki.se Keywords - aging, mouse model, cellular senescence, pulmonary fibrosis, antifibrotics, senolytic 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/ For media inquiries, please contact media@impactjournals.com.

Aging-US
Senescence and Senotherapies in Biliary Atresia and Biliary Cirrhosis

Aging-US

Play Episode Listen Later Jun 28, 2023 3:30


A new research paper was published in Aging (Aging-US) Volume 15, Issue 11, entitled, “Senescence and senotherapies in biliary atresia and biliary cirrhosis.” Premature senescence occurs in adult hepatobiliary diseases and worsens the prognosis through deleterious liver remodeling and hepatic dysfunction. Senescence might also arise in biliary atresia (BA), the first cause of pediatric liver transplantation. Alternatives to transplantation are needed. In this new study, researchers Giulia Jannone, Eliano Bonaccorsi Riani, Catherine de Magnée, Roberto Tambucci, Jonathan Evraerts, Joachim Ravau, Pamela Baldin, Caroline Bouzin, Axelle Loriot, Laurent Gatto, Anabelle Decottignies, Mustapha Najimi, and Etienne Marc Sokal from the Université catholique de Louvain in Brussels, Belgium, aimed to investigate premature senescence in BA and to assess senotherapies in a preclinical model of biliary cirrhosis. “As there is a need for new therapies to avoid or delay liver transplantation in pediatric biliary cirrhosis, the aim of our work was to investigate premature senescence in BA through a multi-technical approach and to assess senotherapies in a preclinical model of biliary cirrhosis.” BA liver tissues were prospectively obtained at hepatoportoenterostomy (n=5) and liver transplantation (n=30) and compared to controls (n=10). Senescence was investigated through spatial whole transcriptome analysis, SA-β-gal activity, p16 and p21 expression, γ-H2AX and senescence-associated secretory phenotype (SASP). Human allogenic liver-derived progenitor cells (HALPC) or dasatinib and quercetin (D+Q) were administered to two-month-old Wistar rats after bile duct ligation (BDL). Advanced premature senescence was evidenced in BA livers from early stage and continued to progress until liver transplantation. Senescence and SASP were predominant in cholangiocytes, but also present in surrounding hepatocytes. HALPC but not D+Q reduced the early marker of senescence p21 in BDL rats and improved biliary injury (serum γGT and Sox9 expression) and hepatocytes mass loss (Hnf4a). “BA livers displayed advanced cellular senescence at diagnosis that continued to progress until liver transplantation. HALPC reduced early senescence and improved liver disease in a preclinical model of BA, providing encouraging preliminary results regarding the use of senotherapies in pediatric biliary cirrhosis.” DOI - https://doi.org/10.18632/aging.204700 Corresponding author - Giulia Jannone - giulia.jannone@uclouvain.be Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204700 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, senescence, senotherapy, liver, biliary cirrhosis, biliary atresia 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

Rational Wellness Podcast
Longevity Breakthroughs with Chris Mirabile: Rational Wellness Podcast 313

Rational Wellness Podcast

Play Episode Listen Later Jun 21, 2023 58:16


Chris Mirabile discusses Longevity Breakthroughs with Dr. Ben Weitz. [If you enjoy this podcast, please give us a rating and review on Apple Podcasts, so more people will find The Rational Wellness Podcast. Also check out the video version on my WeitzChiro YouTube page.]    Podcast Highlights 1:09  Chris noted that his interest in health started when he was 12 years old when he saw a Men's Health magazine and got interested in building his body up.  Then he started to feel faint and dizzy and had a seizure and discovered that he had a brain tumor.  He had surgery that saved his life and this fueled his desire to take control of his life and become an entrepreneur and this also planted the seed for his interest in longevity that has blossomed into his current company, NOVOS. 4:19  Chris was in the technology business, but in his personal life he was focused on health and he was into biohacking.  He experimented with nutritional supplements and various sleep, diet, and exercise routines. He was experimenting with measuring various methods of measuring biological outputs.  About 10 years ago he came across a seminal paper in the journal Cell from 2013: The Hallmarks of Aging (López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013 Jun 6;153(6):1194-217. doi: 10.1016/j.cell.2013.05.039). This paper was updated in 2023 with 3 additional Hallmarks of Aging: An Expanding Universe. (López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: An expanding universe. Cell. 2023 Jan 19;186(2):243-278). 8:18  Chris's personal diet and lifestyle choices for healthy living include what he calls the longevity diet, which is a modified Mediterranean diet that reduces the intake of wheat and grains and increases the intake of vegetables, mushrooms, and legumes.  He is on the lower end of the carb scale of this longevity diet, though not close to ketogenic. He minimizes his saturate fat intake because he notices when his saturated fat intake goes up, his LDL cholesterol levels go up significantly. He does intermittent fasting, following a 16:8 or even a 19:5.  His eating window is typically between 2 pm and 8 pm.  He admits it would be better if this window were 9 am to 5 pm, since you tend to be more insulin sensitive in the morning, but he has trouble maintaining that, since he is not that hungry when he wakes up. Every so often he does a 24 hour fast.  He starts and ends each day with a 2 mile walk.  Six days a week he will work out for 45 minutes to an hour. Three days he will doing weightlifting and the other 3 days he will do a more intense form of cardio.  Sundays he will rest, though he still might walk or go on an easy bike ride. He notices that after not working out on Sundays, his HRV will pick back up, which he monitors with his Oura ring or his Apple watch. He takes a high quality multivitamin/mineral and uses a salt that is half sodium and half potassium, since most of us do not get enough potassium and this keeps Chris's blood pressure in a healthy range. 17:58  The Hallmarks of Aging.  The first Hallmark of Aging is mitochondrial dysfunction.  As we age, we have fewer mitochondria per cell, and the mitochondria that we have in each cell are less efficient, which means that we're able to less efficiently produce the energy, and as a result, our tissues and our organs are not functioning as well as they otherwise would.  A number of ingredients in the NOVOS core product that Chris  developed support mitochondrial health, including magnesium malate, glycine, calcium-alpha-ketoglutarate, fisetin, glucosamine, vitamin C and pterostilbene.  20:58  Cellular senescence. There are cells in the body that are no longer functioning normally, which are referred to as zombie cells and they secrete something called a SASP (senescence-associated secretory phenotype), which are inflammatory molecules that impact nearby cells and cause them to become senescen...

Aging-US
Effects of Zoledronic Acid on Senescence and SASP Markers

Aging-US

Play Episode Listen Later May 15, 2023 3:43


A new research paper was published on the cover of Aging (Aging-US) Volume 15, Issue 9, entitled, “In vitro and in vivo effects of zoledronic acid on senescence and senescence-associated secretory phenotype markers.” Zoledronic acid has been found to reduce fracture risk and, in some studies, to decrease mortality in humans and extend lifespan and healthspan in animals. Because senescent cells accumulate with aging and contribute to multiple comorbidities, the non-skeletal actions of zoledronic acid could be due to senolytic (killing of senescent cells) or senomorphic (inhibition of the secretion of the senescence-associated secretory phenotype (SASP)) actions. In this new study, researchers Parinya Samakkarnthai, Dominik Saul, Lei Zhang, Zaira Aversa, Madison L. Doolittle, Jad G. Sfeir, Japneet Kaur, Elizabeth J. Atkinson, James R. Edwards, Graham G. Russell, Robert J. Pignolo, James L. Kirkland, Tamar Tchkonia, Laura J. Niedernhofer, David G. Monroe, Nathan K. Lebrasseur, Joshua N. Farr, Paul D. Robbins, and Sundeep Khosla from the Mayo Clinic, Phramongkutklao Hospital and College of Medicine, Eberhard Karls University, University of Minnesota, University of Oxford, and University of Sheffield tested the above hypothesis using multiple complementary approaches (in vitro, in vivo, and in silico) to evaluate possible effects of zoledronic acid on modulating cellular senescence. The researchers first performed in vitro senescence assays using human lung fibroblasts and DNA repair-deficient mouse embryonic fibroblasts, which demonstrated that zoledronic acid killed senescent cells with minimal effects on non-senescent cells. Next, in aged mice treated with zoledronic acid or vehicle for 8 weeks, zoledronic acid significantly reduced circulating SASP factors, including CCL7, IL-1β, TNFRSF1A, and TGFβ1 and improved grip strength. Analysis of publicly available RNAseq data from CD115+ (CSF1R/c-fms+) pre-osteoclastic cells isolated from mice treated with zoledronic acid demonstrated a significant downregulation of senescence/SASP genes (SenMayo). To establish that these cells are potential senolytic/senomorphic targets of zoledronic acid, the team used single cell proteomic analysis (cytometry by time of flight [CyTOF]) and demonstrated that zoledronic acid significantly reduced the number of pre-osteoclastic (CD115+/CD3e-/Ly6G-/CD45R-) cells and decreased protein levels of p16, p21, and SASP markers in these cells without affecting other immune cell populations. “Collectively, our findings demonstrate that zoledronic acid has senolytic effects in vitro and modulates senescence/SASP biomarkers in vivo. These data point to the need for additional studies testing zoledronic acid and/or other bisphosphonate derivatives for senotherapeutic efficacy.” DOI - https://doi.org/10.18632/aging.204701 Corresponding author - Sundeep Khosla - khosla.sundeep@mayo.edu 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

Aging-US
The Senescence-Associated Secretory Phenotype Induces Neuroendocrine Transdifferentiation

Aging-US

Play Episode Listen Later May 12, 2023 3:21


A new editorial paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 8, entitled, “The senescence-associated secretory phenotype induces neuroendocrine transdifferentiation.” In this editorial, researchers Anda Huna, Nadine Martin and David Bernard from the Université de Lyon discuss the senescence-associated secretory phenotype (SASP). SASP, in addition to stable proliferation arrest, is one of the most remarkable characteristics of senescent cells. Indeed, these cells secrete a variety of factors including cytokines, growth factors and matrix metalloproteases among others. In response to stress, through their SASP, senescent cells are able to modify and instruct their microenvironment. “The SASP is known to have several, sometimes contradictory, effects on phenotypes, including the induction or reinforcement of senescence in neighboring cells, promotion or inhibition of stemness, modification of extracellular matrix, activation or inhibition of immune responses and induction of epithelial-mesenchymal transition and cell migration.” Although cellular senescence and its SASP can initially display some beneficial effects, for instance favoring wound healing or blocking tumor initiation, accumulation of senescent cells and their secretome during aging or chronic stresses (tobacco, obesity, alcohol among others) plays a significant role in promoting aging-associated features and pathologies, like fibrosis, steatosis, chronic inflammation or cancer. In the context of cancer, senescence initially has an antitumoral role, as it promotes proliferation arrest and favors an anti-tumoral immune surveillance in response to oncogenic stress or DNA damage accumulation. However, SASP plays a dual role in tumor initiation and progression, as it first has a tumor suppressive action by reinforcing senescence in neighboring cells and recruiting immune cells, but also plays a tumor promoting role by promoting stemness, epithelial-mesenchymal transition and cell migration and by inhibiting immune responses. “Overall our work reveals a new effect of senescent cells and their SASP in tumors and offers new insights into NED [neuroendocrine transdifferentiation] in breast and prostate cancer biology. It also provides a new vision of the contribution of senescent cells and their SASP to aging-related pathologies, which could involve NED induction in some contexts.” DOI - https://doi.org/10.18632/aging.204669 Corresponding author - David Bernard - david.bernard@lyon.unicancer.fr Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204669 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, cellular senescence, aging, cancer, NF-κB, calcium signaling 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

Aging-US
A Chronic Wound Model to Investigate Skin Cellular Senescence

Aging-US

Play Episode Listen Later May 1, 2023 3:05


A new research paper was published on the cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 8, entitled, “A chronic wound model to investigate skin cellular senescence.” Wound healing is an essential physiological process for restoring normal skin structure and function post-injury. The role of cellular senescence, an essentially irreversible cell cycle state in response to damaging stimuli, has emerged as a critical mechanism in wound remodeling. Transiently-induced senescence during tissue remodeling has been shown to be beneficial in the acute wound healing phase. In contrast, persistent senescence, as observed in chronic wounds, contributes to delayed closure. In this new study, researchers Saranya P. Wyles, Parisa Dashti, Tamar Pirtskhalava, Burak Tekin, Christina Inman, Lilian Sales Gomez, Anthony B. Lagnado, Larissa Prata, Diana Jurk, João F. Passos, Tamar Tchkonia, and James L. Kirkland from the Mayo Clinic in Rochester, Minnesota, describe a chronic wound murine model and its cellular senescence profile, including the senescence-associated secretory phenotype. “Herein we hypothesize that persistent senescent cell accumulation contributes to delayed healing in chronic wounds.” This study presents a novel oxidative stress-induced chronic murine wound mouse model in which there is capacity to target aberrant senescent cell expression. Pharmacological manipulation of oxidative stress can influence wound healing and result in delayed wound closure, which offers the opportunity to characterize cellular senescence in late stages of wound healing. The molecular and histological profiles of senescent cells in the epidermis and dermis demonstrate the adverse influence of SASP factors in the chronic wound bed, a new avenue for root-cause, targeted therapeutic interventions. “To our knowledge, this study is the first chronic wound murine model to profile the effects of the chronic cellular senescence that is linked to delayed wound healing. This may have implications for developing interventions that target cellular senescence for chronic or stalled wounds as a root cause-driven therapeutic strategy.” DOI: https://doi.org/10.18632/aging.204667 Corresponding Authors: James L. Kirkland - kirkland.james@mayo.edu, and Tamar Tchkonia - tchkonia.tamar@mayo.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204667 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, wound healing, cellular senescence, chronic wound, re-epithelization, skin 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

Aging-US
A Promising Approach to Preventing Periodontitis

Aging-US

Play Episode Listen Later Mar 24, 2023 7:20


Blog summary of a research paper published in Volume 15, Issue 5 of Aging (Aging-US): “Cellular senescence with SASP in periodontal ligament cells triggers inflammation in aging periodontal tissue.” _____________________________________________ Repercussions of poor dental health aren't limited to mere social stigmas. Poor dental health can impart serious consequences on an individual's overall health. Periodontal disease broadly refers to any disease that affects the gums and the surrounding tissues that support the teeth, including the periodontal ligament (PDL) and alveolar bone. Periodontal disease can increase the risk of heart disease, stroke and diabetes by allowing bacteria to enter the bloodstream, causing inflammation and organ damage. Periodontitis is a more advanced stage of periodontal disease. It is thought to be the most common infectious disease in the United States—affecting more than 40% of adults over 30 years old. Previous research has suggested that aging is a significant risk factor for periodontitis, although the underlying mechanisms are unclear. “The direct cause of periodontitis is periodontopathic bacteria, while various environmental factors affect the severity of periodontitis. Previous epidemiological studies have shown positive correlations between aging and periodontitis. However, whether and how aging is linked to periodontal health and disease in biological processes is poorly understood.” Full blog - https://aging-us.org/2023/03/a-promising-approach-to-preventing-periodontitis/ DOI - https://doi.org/10.18632/aging.204569 Corresponding author - Motozo Yamashita - yamashita.motozou.dent@osaka-u.ac.jp Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204569 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, cellular senescence, periodontitis, periodontal ligament, SASP, microRNAs, SIRT1 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

Aging-US
Senescence-Associated Exosomes Transfer Fibrosis to Neighboring Cells

Aging-US

Play Episode Listen Later Mar 17, 2023 4:22


A new research paper was published in Aging (Aging-US) Volume 15, Issue 5, entitled, “Senescence-associated exosomes transfer miRNA-induced fibrosis to neighboring cells.” Radiation-induced fibrosis is a common side effect of radiotherapy, which is the most common treatment for cancer. However, radiation also causes p53-mediated cell cycle arrest, prolonged expression of p21, and the development of senescence in normal cells that reside in irradiated tissues. Bone marrow-derived mesenchymal stem cells (MSCs) accumulate in primary tumor sites because of their natural tropism for inflammatory and fibrotic tissues. MSCs are extremely sensitive to low doses of ionizing radiation and acquire senescence as a result of bystander radiation effects. Senescent cells remain metabolically active but develop a potent senescence-associated secretory phenotype (SASP) that correlates to hyperactive secretion of cytokines, pro-fibrotic growth factors, and exosomes (EXOs). Integrative pathway analysis has highlighted that radiation-induced senescence significantly enriched cell-cycle, extracellular matrix, transforming growth factor-β (TGF-β) signaling, and vesicle-mediated transport genes in MSCs. EXOs are cell-secreted nanovesicles (a subclass of small extracellular vesicles) that contain biomaterials—proteins, RNAs, microRNAs (miRNAs)—that are critical in cell-cell communication. miRNA content analysis of secreted EXOs further revealed that radiation-induced senescence uniquely altered miRNA profiles. “In fact, several of the standout miRNAs directly targeted TGF-β or downstream genes.” In this new study, researchers Amy H. Lee, Deepraj Ghosh, Ivy L. Koh, and Michelle R. Dawson from Brown University further treated normal MSCs with senescence-associated EXOs (SA-EXOs) to examine bystander effects of radiation-induced senescence. The researchers found that these modulated genes were related to TGF-β pathway and elevated both alpha smooth muscle actin (protein increased in senescent, activated cells) and Ki-67 (proliferative marker) expression in SA-EXO treated MSCs compared to untreated MSCs. They revealed that SA-EXOs possess unique miRNA content that influence myofibroblast phenotypes via TGF-β pathway activation. This highlights that SA-EXOs are potent SASP factors that play a large role in cancer-related fibrosis. “Our integrated omics and EXO microarray analyses show that senescent MSCs possess differential transcriptional genes and secrete vesicles that contain unique post-transcriptional cargo. We subsequently demonstrated that these EXO miRNAs can play important roles in cell-cell communication during disease progression.” Paper: DOI: https://doi.org/10.18632/aging.204539 Corresponding Author: Michelle R. Dawson - michelle_dawson@brown.edu Keywords: radiation-induced senescence, exosomes (EXOs), microRNA (miRNA), transforming growth factor-β (TGF-β), mesenchymal stem cells (MSCs) 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

Aging-US
Clearance of p16Ink4a-positive Cells in Mice: Effects on β-cell Mass and Proliferation

Aging-US

Play Episode Listen Later Jan 31, 2023 3:51


A new research paper was published on the cover of Aging (Aging-US)) Volume 15, Issue 2, entitled, “Clearance of p16Ink4a-positive cells in a mouse transgenic model does not change β-cell mass and has limited effects on their proliferative capacity.” Type 2 diabetes is partly characterized by decreased β-cell mass and function which have been linked to cellular senescence. Despite a low basal proliferative rate of adult β-cells, they can respond to growth stimuli, but this proliferative capacity decreases with age and correlates with increased expression of senescence effector, p16Ink4a. In a new study, researchers Nadine Bahour, Lucia Bleichmar, Cristian Abarca, Emeline Wilmann, Stephanie Sanjines, and Cristina Aguayo-Mazzucato from the Joslin Diabetes Center at Harvard Medical School hypothesized that selective deletion of p16Ink4a-positive cells would enhance the proliferative capacity of the remaining β-cells due to the elimination of the local senescence-associated secretory phenotype (SASP). “We aimed to investigate the effects of p16Ink4a-positive cell removal on the mass and proliferative capacity of remaining β-cells using INK-ATTAC mice as a transgenic model of senolysis.” Clearance of p16Ink4a-positive subpopulation was tested in mice of different ages, males and females, and with two different insulin resistance models: high-fat diet (HFD) and insulin receptor antagonist (S961). Clearance of p16Ink4a-positive cells did not affect the overall β-cell mass. β-cell proliferative capacity negatively correlated with cellular senescence load and clearance of p16Ink4a positive cells in 1-year-old HFD mice improved β-cell function and increased proliferative capacity in a subset of animals. Single-cell sequencing revealed that the targeted p16Ink4a subpopulation of β-cells is non-proliferative and non-SASP producing whereas additional senescent subpopulations remained contributing to continued local SASP secretion. “In conclusion, deletion of p16Ink4a cells did not negatively impact beta-cell mass and blood glucose under basal and HFD conditions and proliferation was restored in a subset of HFD mice opening further therapeutic targets in the treatment of diabetes.” DOI: https://doi.org/10.18632/aging.204483 Corresponding Author: Cristina Aguayo-Mazzucato - cristina.aguayo-mazzucato@joslin.harvard.edu Keywords: beta cells, mass, proliferation, senolysis, senescence Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204483 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://youtube.com/Aging-US LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Epigenetics Podcast
Genome Organization Mediated by RNA Polymerase II (Argyrys Papantonis)

Epigenetics Podcast

Play Episode Listen Later Dec 15, 2022 43:33


In this episode of the Epigenetics Podcast, we caught up with Akis Papantonis from the University Medical Center Göttingen to talk about his work on genome organisation mediated by RNA Polymerase II. The research of the Papantonis Laboratory focuses on investigating how environmental signalling stimuli are integrated by chromatin to control homeostatic to deregulated functional transitions. In more detail, the team is interested in how dynamic higher-order regulatory networks are influenced by the underlying linear DNA fiber. The ultimate goal of the laboratory is to understand general rules governing transcriptional and chromatin homeostasis and finally, how those rules might affect development, ageing or malignancies.   References Larkin, J. D., Cook, P. R., & Papantonis, A. (2012). Dynamic reconfiguration of long human genes during one transcription cycle. Molecular and cellular biology, 32(14), 2738–2747. https://doi.org/10.1128/MCB.00179-12 Diermeier, S., Kolovos, P., Heizinger, L., Schwartz, U., Georgomanolis, T., Zirkel, A., Wedemann, G., Grosveld, F., Knoch, T. A., Merkl, R., Cook, P. R., Längst, G., & Papantonis, A. (2014). TNFα signalling primes chromatin for NF-κB binding and induces rapid and widespread nucleosome repositioning. Genome biology, 15(12), 536. https://doi.org/10.1186/s13059-014-0536-6 Sofiadis, K., Josipovic, N., Nikolic, M., Kargapolova, Y., Übelmesser, N., Varamogianni-Mamatsi, V., Zirkel, A., Papadionysiou, I., Loughran, G., Keane, J., Michel, A., Gusmao, E. G., Becker, C., Altmüller, J., Georgomanolis, T., Mizi, A., & Papantonis, A. (2021). HMGB1 coordinates SASP-related chromatin folding and RNA homeostasis on the path to senescence. Molecular systems biology, 17(6), e9760. https://doi.org/10.15252/msb.20209760 Enhancer-promoter contact formation requires RNAPII and antagonizes loop extrusion. Shu Zhang, Nadine Übelmesser, Mariano Barbieri, Argyris Papantonis. bioRxiv 2022.07.04.498738; doi: https://doi.org/10.1101/2022.07.04.498738   Related Episodes Chromatin Organization During Development and Disease (Marieke Oudelaar) Biophysical Modeling of 3-D Genome Organization (Leonid Mirny) Hi-C and Three-Dimensional Genome Sequencing (Erez Lieberman Aiden)   Contact Epigenetics Podcast on Twitter Epigenetics Podcast on Instagram Epigenetics Podcast on Mastodon Active Motif on Twitter Active Motif on LinkedIn Email: podcast@activemotif.com

Aging-US
Press Release: Downregulation of SASP by SFRP4 Knockdown Helps Prevent Skin Aging

Aging-US

Play Episode Listen Later Oct 31, 2022 3:55


A new research paper was published on the cover of Aging (listed as "Aging (Albany NY)" by Medline/PubMed and "Aging-US" by Web of Science) Volume 14, Issue 20, entitled, “Downregulation of senescence-associated secretory phenotype by knockdown of secreted frizzled-related protein 4 contributes to the prevention of skin aging.” There is growing evidence that the appearance and texture of the skin that is altered during the aging process are considerably enhanced by the accumulation of senescent dermal fibroblasts. These senescent cells magnify aging via an inflammatory, histolytic, and senescence-associated secretory phenotype (SASP). Secreted frizzled-related protein 4 (SFRP4) was previously determined to be expressed in dermal fibroblasts of aging skin, and its increased expression has been shown to promote cellular senescence. However, its role in the SASP remains unknown. In this new study, researchers Kento Takaya, Toru Asou and Kazuo Kishi from Keio University School of Medicine's Department of Plastic and Reconstructive Surgery investigated the classical model of skin fibroblasts based on Hayflick's mitotic limit, the observation of SFRP4 expression in replicating senescent cells, and the effect of regulating this on the suppression of SASP and aging skin. “These results may contribute to the development of new therapies to ameliorate skin aging.” The researchers found that SFRP4 was significantly expressed in p16ink4a-positive human skin fibroblasts and that treatment with recombinant SFRP4 promoted SASP and senescence, whereas siRNA knockdown of SFRP4 suppressed SASP. They also found that knockdown of SFRP4 in mouse skin ameliorates age-related reduction of subcutaneous adipose tissue, panniculus carnosus muscle layer, and thinning and dispersion of collagen fibers. These findings suggest a potential candidate for the development of new skin rejuvenation therapies that suppress SASP. “This study shows that SFRP4, which is specifically expressed in aged p16ink4a-positive skin fibroblasts, contributes to SASP, and that treatment with SFRP4 causes worsening of this phenotype. To the best of our knowledge, the present study is the first to report that the suppression of SFRP4 expression in vivo ameliorates skin aging-related phenotypes, that is, adipose tissue atrophy and collagen fiber thinning, via SASP suppression.” DOI: https://doi.org/10.18632/aging.204273 Corresponding Author: Kento Takaya - Email: kento-takaya312@keio.jp Keywords: skin, fibroblast, SASP, SFRP4 Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204273 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. Aging (Aging-US) Journal Office 6666 E. Quaker Str., Suite 1B Orchard Park, NY 14127 Phone: 1-800-922-0957, option 1

SSSF Rangetime
S2 E7: The Multi-Discipline Athlete

SSSF Rangetime

Play Episode Listen Later Aug 5, 2022 16:37


We are joined by Scott Lueders a parent and a coach, as well as his daughter, SCTP and SASP athlete of many years, Bailey Lueders. Bailey is 2021's runner up in the Top Gun Challenge two years in a row and that makes her the dominating female athlete as well. Multi-discipline athletes at Nationals compete in Trap, Skeet, Sporting Clays, Iron sight pistol (Rimfire or Centerfire), fastest rifle time, and 1911 with their scores from each event being compiled to calculate the Top Gun Challenge Champion.

Modern Healthspan
Using Exosomes To Release Youthful Factors Prof Paul Robbins Ep 5

Modern Healthspan

Play Episode Listen Later Jul 3, 2022 5:49


In this video Professor Robbins discusses the work his lab is doing with Exosomes or EV (Extra-Cellular Vesicles) and how these can impact senescent cells by suppressing SASP as senomorphics Dr. Robbins is a Professor of Biochemistry, Molecular Biology and Biophysics and Associate Director of the Institute on the Biology of Aging and Metabolism (iBAM) at the University of Minnesota. He was part of a collaborative team that was the first to identify senotherapeutic compounds, able to reduce the senescent cell burden and extend healthspan and lifespan in mouse models that are now in more than 15 clinical trials. Professor Robbins' page at University of Minnesota https://robbins.umn.edu/dr-paul-robbins-phd Institute of the Biology of Aging and Metabolism If you would like to support our channel, we'd love a coffee ☕…thank you! https://www.buymeacoffee.com/mhealthspan You can also find us on YouTube at https://www.youtube.com/c/modernhealthspan 15% off Bulletproof products at https://www.bulletproof.com/ with discount code HEALTHSPAN15. Renue By Science 10% discount code MHS at https://renuebyscience.com/all-products-2/ 10% off all products at DoNotAge with code MODERNHEALTHSPAN at https://donotage.org/

Authentic Biochemistry
CytoEpigenetics XV.An AMPK phosphorylation cascade promoting mTOR pro-translational induction of NFkappa-B SASP transcription is modulated by NAD+ Sirtuin and PARP during Chromatin retailoring.DJGPhD

Authentic Biochemistry

Play Episode Listen Later May 28, 2022 29:59


References Dr Guerra's synthesis of the relevant literature BioEssays, Volume: 39, Issue: 5, First published: 20 February 2017. Front Cardiovasc Med. 2020; 7: 2. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

Modern Healthspan
The Future of Aging Dr. Kirkland Interview Series Ep 6

Modern Healthspan

Play Episode Listen Later Mar 9, 2022 9:01


In this video Dr. Kirkland talks about the future of aging and how the biology of aging affects everyone and should not be thought of as only relevant to older people. He also discusses the path of bringing senolytics to wider use. Dr. James Kirkland is Director of the Robert and Arlene Kogod Center on Aging at Mayo Clinic and Noaber Foundation Professor of Aging Research. Dr. Kirkland's research focuses on cellular senescence, age-related adipose tissue and metabolic dysfunction, and development of agents and strategies for targeting fundamental aging mechanisms to treat age-related chronic diseases and disabilities and to extend healthspan. He published the first article about drugs that clear senescent cells, senolytic agents. A novel, mechanism-based, hypothesis-driven drug development paradigm was used to discover senolytic drugs. Based on the observation that senescent cells release factors that cause apoptosis of the cells around them, yet are themselves resistant to apoptosis, Dr. Kirkland hypothesized that senescent cells utilize senescent cell anti-apoptotic pathways (SCAPs) for protection from their own senescence-associated secretory phenotype (SASP). Using bioinformatics analyses of senescent vs. non-senescent cells and RNA interference, Dr. Kirkland identified these SCAPs and verified their importance for senescent cell survival. Dr. Kirkland used bioinformatics approaches to identify agents that target key nodes across the SCAP network and demonstrated these drugs are senolytic in rodent and human cultured cells and mice in vivo. These senolytic drugs include Dasatinib (D), Quercetin (Q), Fisetin, Navitoclax, and related compounds. Dr. Kirkland showed these agents delay, prevent, or alleviate multiple disorders in mouse models of human chronic diseases and aging phenotypes. Conditions alleviated in mouse models include frailty, diabetes, hepatic steatosis, cirrhosis, renal dysfunction, neuropsychiatric disorders, dementias, pulmonary fibrosis, osteoporosis, osteoarthritis, retinal degeneration, diastolic dysfunction, cardiac ischemia, vascular hyporeactivity, infertility, and skin disorders, among others. He demonstrated that intermittent, orally administered senolytics reduce senescent cell abundance in adipose tissue and blood markers of senescent cell burden in blood of patients with diabetic kidney disease. He and collaborators found that a brief course of senolytics enhances physical function and reduces frailty in patients with idiopathic pulmonary fibrosis, a fatal, cellular-senescence-driven disease for which available treatments have been unsatisfactory. Multiple clinical trials are currently underway of the senolytics that Dr. Kirkland discovered. He is a scientific advisory board member for several companies and academic organizations. In addition to being President-Elect of AFAR, he has been a member of the National Advisory Council on Aging of the National Institutes of Health, and past chair of the Biological Sciences Section of the Gerontological Society of America. He holds honorary appointments at Boston University and the University of Groningen in the Netherlands. He is a board-certified specialist in internal medicine, geriatrics, and endocrinology and metabolism. If you would like to support our channel, we'd love a coffee ☕…thank you! https://www.buymeacoffee.com/mhealthspan You can also find us on YouTube at https://www.youtube.com/c/modernhealthspan

Modern Healthspan
Lifestyles To Reduce Senescent Burden & Measuring Panel Dr. James Kirkland Interview Series Ep 5

Modern Healthspan

Play Episode Listen Later Mar 6, 2022 8:00


In this video Dr. Kirkland talks about what we can do to reduce our senescent cell burden with lifestyle choices and how there is a grouping of health organizations measuring health markers across multiple trials to gather data on aging. Dr. James Kirkland is Director of the Robert and Arlene Kogod Center on Aging at Mayo Clinic and Noaber Foundation Professor of Aging Research. Dr. Kirkland's research focuses on cellular senescence, age-related adipose tissue and metabolic dysfunction, and development of agents and strategies for targeting fundamental aging mechanisms to treat age-related chronic diseases and disabilities and to extend healthspan. He published the first article about drugs that clear senescent cells, senolytic agents. A novel, mechanism-based, hypothesis-driven drug development paradigm was used to discover senolytic drugs. Based on the observation that senescent cells release factors that cause apoptosis of the cells around them, yet are themselves resistant to apoptosis, Dr. Kirkland hypothesized that senescent cells utilize senescent cell anti-apoptotic pathways (SCAPs) for protection from their own senescence-associated secretory phenotype (SASP). Using bioinformatics analyses of senescent vs. non-senescent cells and RNA interference, Dr. Kirkland identified these SCAPs and verified their importance for senescent cell survival. Dr. Kirkland used bioinformatics approaches to identify agents that target key nodes across the SCAP network and demonstrated these drugs are senolytic in rodent and human cultured cells and mice in vivo. These senolytic drugs include Dasatinib (D), Quercetin (Q), Fisetin, Navitoclax, and related compounds. Dr. Kirkland showed these agents delay, prevent, or alleviate multiple disorders in mouse models of human chronic diseases and aging phenotypes. Conditions alleviated in mouse models include frailty, diabetes, hepatic steatosis, cirrhosis, renal dysfunction, neuropsychiatric disorders, dementias, pulmonary fibrosis, osteoporosis, osteoarthritis, retinal degeneration, diastolic dysfunction, cardiac ischemia, vascular hyporeactivity, infertility, and skin disorders, among others. He demonstrated that intermittent, orally administered senolytics reduce senescent cell abundance in adipose tissue and blood markers of senescent cell burden in blood of patients with diabetic kidney disease. He and collaborators found that a brief course of senolytics enhances physical function and reduces frailty in patients with idiopathic pulmonary fibrosis, a fatal, cellular-senescence-driven disease for which available treatments have been unsatisfactory. Multiple clinical trials are currently underway of the senolytics that Dr. Kirkland discovered. He is a scientific advisory board member for several companies and academic organizations. In addition to being President-Elect of AFAR, he has been a member of the National Advisory Council on Aging of the National Institutes of Health, and past chair of the Biological Sciences Section of the Gerontological Society of America. He holds honorary appointments at Boston University and the University of Groningen in the Netherlands. He is a board-certified specialist in internal medicine, geriatrics, and endocrinology and metabolism. If you would like to support our channel, we'd love a coffee ☕…thank you! https://www.buymeacoffee.com/mhealthspan You can also find us on YouTube at https://www.youtube.com/c/modernhealthspan

Modern Healthspan
Fisetin, Quercetin & Dasatinib in Clinical Trials Dr. James Kirkland Interview Series Ep 4

Modern Healthspan

Play Episode Listen Later Mar 2, 2022 10:08


In this video Dr. Kirkland talks about the senolytics that the Mayo Clinic is using in the on going trials, dasatinib, Fisetin and Quercetin. He also talks about the way the work and the schedule to taking them Dr. James Kirkland is Director of the Robert and Arlene Kogod Center on Aging at Mayo Clinic and Noaber Foundation Professor of Aging Research. Dr. Kirkland's research focuses on cellular senescence, age-related adipose tissue and metabolic dysfunction, and development of agents and strategies for targeting fundamental aging mechanisms to treat age-related chronic diseases and disabilities and to extend healthspan. He published the first article about drugs that clear senescent cells, senolytic agents. A novel, mechanism-based, hypothesis-driven drug development paradigm was used to discover senolytic drugs. Based on the observation that senescent cells release factors that cause apoptosis of the cells around them, yet are themselves resistant to apoptosis, Dr. Kirkland hypothesized that senescent cells utilize senescent cell anti-apoptotic pathways (SCAPs) for protection from their own senescence-associated secretory phenotype (SASP). Using bioinformatics analyses of senescent vs. non-senescent cells and RNA interference, Dr. Kirkland identified these SCAPs and verified their importance for senescent cell survival. Dr. Kirkland used bioinformatics approaches to identify agents that target key nodes across the SCAP network and demonstrated these drugs are senolytic in rodent and human cultured cells and mice in vivo. These senolytic drugs include Dasatinib (D), Quercetin (Q), Fisetin, Navitoclax, and related compounds. Dr. Kirkland showed these agents delay, prevent, or alleviate multiple disorders in mouse models of human chronic diseases and aging phenotypes. Conditions alleviated in mouse models include frailty, diabetes, hepatic steatosis, cirrhosis, renal dysfunction, neuropsychiatric disorders, dementias, pulmonary fibrosis, osteoporosis, osteoarthritis, retinal degeneration, diastolic dysfunction, cardiac ischemia, vascular hyporeactivity, infertility, and skin disorders, among others. He demonstrated that intermittent, orally administered senolytics reduce senescent cell abundance in adipose tissue and blood markers of senescent cell burden in blood of patients with diabetic kidney disease. He and collaborators found that a brief course of senolytics enhances physical function and reduces frailty in patients with idiopathic pulmonary fibrosis, a fatal, cellular-senescence-driven disease for which available treatments have been unsatisfactory. Multiple clinical trials are currently underway of the senolytics that Dr. Kirkland discovered. He is a scientific advisory board member for several companies and academic organizations. In addition to being President-Elect of AFAR, he has been a member of the National Advisory Council on Aging of the National Institutes of Health, and past chair of the Biological Sciences Section of the Gerontological Society of America. He holds honorary appointments at Boston University and the University of Groningen in the Netherlands. He is a board-certified specialist in internal medicine, geriatrics, and endocrinology and metabolism. If you would like to support our channel, we'd love a coffee ☕…thank you! https://www.buymeacoffee.com/mhealthspan You can also find us on YouTube at https://www.youtube.com/c/modernhealthspan

Modern Healthspan
Senescent Cells Effect & Benefits of Removing Dr James Kirkland Interview Series Ep 3

Modern Healthspan

Play Episode Listen Later Feb 26, 2022 13:35


In this video Dr. Kirkland talks about how and why senescent cells are formed, how they can be removed and what the benefits of removing them is. Dr. James Kirkland is Director of the Robert and Arlene Kogod Center on Aging at Mayo Clinic and Noaber Foundation Professor of Aging Research. Dr. Kirkland's research focuses on cellular senescence, age-related adipose tissue and metabolic dysfunction, and development of agents and strategies for targeting fundamental aging mechanisms to treat age-related chronic diseases and disabilities and to extend healthspan. He published the first article about drugs that clear senescent cells, senolytic agents. A novel, mechanism-based, hypothesis-driven drug development paradigm was used to discover senolytic drugs. Based on the observation that senescent cells release factors that cause apoptosis of the cells around them, yet are themselves resistant to apoptosis, Dr. Kirkland hypothesized that senescent cells utilize senescent cell anti-apoptotic pathways (SCAPs) for protection from their own senescence-associated secretory phenotype (SASP). Using bioinformatics analyses of senescent vs. non-senescent cells and RNA interference, Dr. Kirkland identified these SCAPs and verified their importance for senescent cell survival. Dr. Kirkland used bioinformatics approaches to identify agents that target key nodes across the SCAP network and demonstrated these drugs are senolytic in rodent and human cultured cells and mice in vivo. These senolytic drugs include Dasatinib (D), Quercetin (Q), Fisetin, Navitoclax, and related compounds. Dr. Kirkland showed these agents delay, prevent, or alleviate multiple disorders in mouse models of human chronic diseases and aging phenotypes. Conditions alleviated in mouse models include frailty, diabetes, hepatic steatosis, cirrhosis, renal dysfunction, neuropsychiatric disorders, dementias, pulmonary fibrosis, osteoporosis, osteoarthritis, retinal degeneration, diastolic dysfunction, cardiac ischemia, vascular hyporeactivity, infertility, and skin disorders, among others. He demonstrated that intermittent, orally administered senolytics reduce senescent cell abundance in adipose tissue and blood markers of senescent cell burden in blood of patients with diabetic kidney disease. He and collaborators found that a brief course of senolytics enhances physical function and reduces frailty in patients with idiopathic pulmonary fibrosis, a fatal, cellular-senescence-driven disease for which available treatments have been unsatisfactory. Multiple clinical trials are currently underway of the senolytics that Dr. Kirkland discovered. He is a scientific advisory board member for several companies and academic organizations. In addition to being President-Elect of AFAR, he has been a member of the National Advisory Council on Aging of the National Institutes of Health, and past chair of the Biological Sciences Section of the Gerontological Society of America. He holds honorary appointments at Boston University and the University of Groningen in the Netherlands. He is a board-certified specialist in internal medicine, geriatrics, and endocrinology and metabolism. If you would like to support our channel, we'd love a coffee ☕…thank you! https://www.buymeacoffee.com/mhealthspan You can also find us on YouTube at https://www.youtube.com/c/modernhealthspan

Modern Healthspan
What Are Senescent Cells Dr James Kirkland Interview Series Ep 2

Modern Healthspan

Play Episode Listen Later Feb 23, 2022 11:32


In this video Dr. Kirkland gives a wide introduction to senescent cells including why we have them, what purpose they serve and what damage they can cause. Dr. James Kirkland is Director of the Robert and Arlene Kogod Center on Aging at Mayo Clinic and Noaber Foundation Professor of Aging Research. Dr. Kirkland's research focuses on cellular senescence, age-related adipose tissue and metabolic dysfunction, and development of agents and strategies for targeting fundamental aging mechanisms to treat age-related chronic diseases and disabilities and to extend healthspan. He published the first article about drugs that clear senescent cells, senolytic agents. A novel, mechanism-based, hypothesis-driven drug development paradigm was used to discover senolytic drugs. Based on the observation that senescent cells release factors that cause apoptosis of the cells around them, yet are themselves resistant to apoptosis, Dr. Kirkland hypothesized that senescent cells utilize senescent cell anti-apoptotic pathways (SCAPs) for protection from their own senescence-associated secretory phenotype (SASP). Using bioinformatics analyses of senescent vs. non-senescent cells and RNA interference, Dr. Kirkland identified these SCAPs and verified their importance for senescent cell survival. Dr. Kirkland used bioinformatics approaches to identify agents that target key nodes across the SCAP network and demonstrated these drugs are senolytic in rodent and human cultured cells and mice in vivo. These senolytic drugs include Dasatinib (D), Quercetin (Q), Fisetin, Navitoclax, and related compounds. Dr. Kirkland showed these agents delay, prevent, or alleviate multiple disorders in mouse models of human chronic diseases and aging phenotypes. Conditions alleviated in mouse models include frailty, diabetes, hepatic steatosis, cirrhosis, renal dysfunction, neuropsychiatric disorders, dementias, pulmonary fibrosis, osteoporosis, osteoarthritis, retinal degeneration, diastolic dysfunction, cardiac ischemia, vascular hyporeactivity, infertility, and skin disorders, among others. He demonstrated that intermittent, orally administered senolytics reduce senescent cell abundance in adipose tissue and blood markers of senescent cell burden in blood of patients with diabetic kidney disease. He and collaborators found that a brief course of senolytics enhances physical function and reduces frailty in patients with idiopathic pulmonary fibrosis, a fatal, cellular-senescence-driven disease for which available treatments have been unsatisfactory. Multiple clinical trials are currently underway of the senolytics that Dr. Kirkland discovered. He is a scientific advisory board member for several companies and academic organizations. In addition to being President-Elect of AFAR, he has been a member of the National Advisory Council on Aging of the National Institutes of Health, and past chair of the Biological Sciences Section of the Gerontological Society of America. He holds honorary appointments at Boston University and the University of Groningen in the Netherlands. He is a board-certified specialist in internal medicine, geriatrics, and endocrinology and metabolism. If you would like to support our channel, we'd love a coffee ☕…thank you! https://www.buymeacoffee.com/mhealthspan You can also find us on YouTube at https://www.youtube.com/c/modernhealthspan

Modern Healthspan
My Theory Of Aging & Unitary Theory Of Fundamental Aging - Dr James Kirkland Interview Series Ep1

Modern Healthspan

Play Episode Listen Later Feb 20, 2022 8:21


In this video Dr. Kirkland explains his theory of aging and discusses the Unitary Theory of Fundamental Aging, which posits that there are underlying pillars of aging which cause the diseases of aging and that are interlinked. Dr. Kirkland offers some examples of these linkages Dr. James Kirkland is Director of the Robert and Arlene Kogod Center on Aging at Mayo Clinic and Noaber Foundation Professor of Aging Research. Dr. Kirkland's research focuses on cellular senescence, age-related adipose tissue and metabolic dysfunction, and development of agents and strategies for targeting fundamental aging mechanisms to treat age-related chronic diseases and disabilities and to extend healthspan. He published the first article about drugs that clear senescent cells, senolytic agents. A novel, mechanism-based, hypothesis-driven drug development paradigm was used to discover senolytic drugs. Based on the observation that senescent cells release factors that cause apoptosis of the cells around them, yet are themselves resistant to apoptosis, Dr. Kirkland hypothesized that senescent cells utilize senescent cell anti-apoptotic pathways (SCAPs) for protection from their own senescence-associated secretory phenotype (SASP). Using bioinformatics analyses of senescent vs. non-senescent cells and RNA interference, Dr. Kirkland identified these SCAPs and verified their importance for senescent cell survival. Dr. Kirkland used bioinformatics approaches to identify agents that target key nodes across the SCAP network and demonstrated these drugs are senolytic in rodent and human cultured cells and mice in vivo. These senolytic drugs include Dasatinib (D), Quercetin (Q), Fisetin, Navitoclax, and related compounds. Dr. Kirkland showed these agents delay, prevent, or alleviate multiple disorders in mouse models of human chronic diseases and aging phenotypes. Conditions alleviated in mouse models include frailty, diabetes, hepatic steatosis, cirrhosis, renal dysfunction, neuropsychiatric disorders, dementias, pulmonary fibrosis, osteoporosis, osteoarthritis, retinal degeneration, diastolic dysfunction, cardiac ischemia, vascular hyporeactivity, infertility, and skin disorders, among others. He demonstrated that intermittent, orally administered senolytics reduce senescent cell abundance in adipose tissue and blood markers of senescent cell burden in blood of patients with diabetic kidney disease. He and collaborators found that a brief course of senolytics enhances physical function and reduces frailty in patients with idiopathic pulmonary fibrosis, a fatal, cellular-senescence-driven disease for which available treatments have been unsatisfactory. Multiple clinical trials are currently underway of the senolytics that Dr. Kirkland discovered. He is a scientific advisory board member for several companies and academic organizations. In addition to being President-Elect of AFAR, he has been a member of the National Advisory Council on Aging of the National Institutes of Health, and past chair of the Biological Sciences Section of the Gerontological Society of America. He holds honorary appointments at Boston University and the University of Groningen in the Netherlands. He is a board-certified specialist in internal medicine, geriatrics, and endocrinology and metabolism. If you would like to support our channel, we'd love a coffee ☕…thank you! https://www.buymeacoffee.com/mhealthspan You can also find us on YouTube at https://www.youtube.com/c/modernhealthspan

Aging-US
Trending With Impact: Radiation, Senescence and Senotherapeutics

Aging-US

Play Episode Listen Later Feb 18, 2022 6:59


Radiation therapy is a highly-effective inducer of cancer cell death. With this being said, radiation has also previously been shown to cause premature senescence in the lung parenchyma. Senescence in cancer cells was previously only thought of as a mechanism capable of suppressing tumor cell proliferation by halting the cell cycle. However, a growing body of evidence shows that senescent cells may play a pro-tumorigenic role in cancer. In the tumor microenvironment, the accumulation of senescent cells can become tumorigenic due to a lack of normal tissue stem cells and due to the expression of the senescence-associated secretory phenotype (SASP). SASP expression is when senescent cells secrete high levels of inflammatory cytokines, immune modulators, growth factors, and proteases. In addition to reinforcing senescence, SASP can create a biological environment that is immuno-suppressed and tumor-permissive. Radiation-induced senescence has previously been shown to have negative impacts on cancer patients. “Cells that have undergone premature senescence due to stress, such as irradiation, are resistant to apoptotic cell death and effectively escape immune surveillance, resulting in their accumulation in tissue over time.” Recently, researchers from the National Cancer Institute investigated the irradiated lung and the impact of radiation-induced senescent parenchymal cells on tumor growth. They also explored three senotherapeutics, rapamycin, INK-128 and ABT-737, for their potential to mitigate radiation-induced senescence. On February 12, 2022, the team's priority research paper was published on the cover of Aging (Aging-US) Volume 14, Issue 3, and entitled, “Senescence-associated tumor growth is promoted by 12-Lipoxygenase.” Full blog - https://www.impactjournals.com/journals/blog/aging/trending-with-impact-radiation-senescence-and-senotherapeutics/ DOI - https://doi.org/10.18632/aging.203890 Corresponding author - Deborah E. Citrin - citrind@mail.nih.gov Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.203890 Keywords - aging, senescence, radiation, senolytic, metastasis, Alox12 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 http://www.Aging-US.com​​ or 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/ Pinterest - https://www.pinterest.com/AgingUS/ Aging-US is published by Impact Journals, LLC: http://www.ImpactJournals.com​​ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Divas puslodes
Krievijas un Ukrainas saspīlētās attiecības ietekmē arī Eiropas Parlamenta dienaskārtību

Divas puslodes

Play Episode Listen Later Feb 16, 2022 54:00


Aizvadīta nedēļa ir bijusi spriedzes pilna. Vairums ziņu ir saistīstas ar Ukrainu, Krieviju un citu valstu reakciju uz notiekošo. Notikumus komentē Eiropas Parlamenta deputātes no Latvijas Inese Vaidere un Dace Melbārde. Ukrainas bruņoto spēku karavīrs pie blindāžas uz sniegotu lauku fona – šādu ilustrāciju Eiropas Parlamenta mājas lapas veidotāji izvēlējušies materiālam par pašreiz Strasbūrā notiekošo parlamenta plenārsesiju. Krievija turpina lēnām, bet nepārtraukti palielināt savu militāro kontingentu Ukrainas robežu tuvumā, un jautājums par plašas karadarbības iespējamību Eiropas Savienības robežu tiešā tuvumā neizbēgami nosaka noskaņojumu vienotās Eiropas likumdevēju forumā.   Kaut, protams, parlaments savā plenārsesijā lemj arī daudzus citus darbakārtības jautājumus: par Eiropas Savienības nozīmīgāko lomu vēža saslimstības apkarošanā, stingrāku rotaļlietu drošības kontroli, vienotu stratēģiju jūras piekrastes izmantošanā atjaunoto energoresursu ražošanai, strādājošo aizsardzību pret bīstamām ķīmiskām vielām, u.t.t. Savu darbu pirmdien, 14. februārī, parlamentārieši uzsāka, atzīmējot divdesmito gadadienu kopš pirmo eiro banknošu un monētu laišanas apgrozībā un turpināja ar Eiropas Centrālās bankas gada pārskata ziņojumu, klātesot bankas prezidentei Kristīnei Lagardai un atbildīgajam Eiropas Komisijas izpildviceprezidentam Valdim Dombrovskim. Krievijas agresija pret Ukrainu ir dienaskārtībā šodien, 16. februārī, kad par šo jautājumu uzstāsies augstais komisārs ārējās un drošības politikas jautājumos Žozeps Borels ar sekojošām plašām debatēm. Jauna rezolūcija par Ukrainu gan nav paredzēta, ciktāl stāvoklis šai ziņā ļoti strauji mainās. Tāpat Eiropas Savienības politika attieksmē pret Krieviju noteikti tiks nozīmīgi skarta debatēs vēlāk šovakar, apspriežot parlamenta Ārlietu komitejas sagatavoto ziņojumu par Eiropas vienotās ārpolitikas īstenošanu, kā arī Ārlietu komitejas Drošības un aizsardzības apakškomitejas ziņojumu par kopīgo drošības un aizsardzības politiku. Sagatavoja Eduards Liniņš.   Eiropas Parlamenta granta projekta „Jaunā Eiropas nākotne” programma.* * Šī publikācija atspoguļo tikai materiāla veidošanā iesaistīto pušu viedokli. Eiropas Parlaments nav atbildīgs par tajā ietvertās informācijas jebkādu izmantošanu.

Aging-US
Aging-US: Senescent Secretory Phenotype Acquisition on Retinal Epithelial Stem Cells

Aging-US

Play Episode Listen Later Sep 27, 2021 1:58


Aging-US published a Special Collection on Eye Disease which included "Effects of senescent secretory phenotype acquisition on human retinal pigment epithelial stem cells" which reported that loss of retinal pigment epithelium (RPE) cells occurs early in AMD, and their transplant has the potential to slow disease progression. Age-related MSC changes involve loss of function and acquisition of a senescence-associated secretory phenotype (SASP). These changes can contribute to the maintenance of a chronic state of low-grade inflammation in tissues and organs. Dr. Cesare Mariotti from The Università Politecnica delle Marche said, "Age-related macular degeneration (AMD) is an eye disorder affecting the elderly which can induce an irreversible loss of central visual function." Age-related macular degeneration (AMD) is one of the most serious and debilitating forms of aging-related eye disease. Smoking, cataract surgery, high BMI and cardiovascular disease are risk factors for AMD, as well as a family history of AMD. No effective treatment is available for neovascular AMD, while anti-VEGFD is the mainstay of treatment for dry AMD. Neovascular AMD and GA are characterized by RPE dysfunction; formation of large confluent drusen and hyperpigmentation seem to be the initial insult. AMD patients show a different phenotype as well as functional changes such as altered autophagy, mitochondrial dysfunction, and susceptibility to oxidative stress. A greater understanding of the molecular pathways that are involved in the various stages of AMD would contribute to the development of innovative therapies. The Mariotti Research Team concluded in their Aging-US Research Output that RPESCs can undergo replicative senescence, which affects their proliferation and differentiation ability. In addition, they acquired the SASP, which probably compounds the inflammatory RPE microenvironment during AMD development and progression. A greater understanding of the role of RPESCs in AMD pathogenesis is needed to find means to control the disease. Full Text - https://www.aging-us.com/article/101624/text Correspondence to: Cesare Mariotti email: mariottiocul@gmail.com Keywords: AMD, RPESCs, age-related diseases, senescence, inflammation About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways. To learn more about Aging-US, please visit http://www.Aging-US.com or connect with @AgingJrnl Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact 18009220957x105 MEDIA@IMPACTJOURNALS.COM

Talks in English
TE 11: A Talk at the Relics Installation at SASP, Lodi

Talks in English

Play Episode Listen Later Sep 25, 2021 35:43


A Talk at the Sacred Relics Installation at SASP, Lodi (California)

Aging-US
Immunosenescence and the Aging Immune System

Aging-US

Play Episode Listen Later Sep 8, 2021 6:18


The immune system is a vast and intricate network. Seven percent of the entire human genome is composed of immune-specific genes. This complex system has important functional and maintenance roles that involve clearing out foreign pathogens and sweeping away dead or dysfunctional cells. As do most human systems, the immune system experiences degradation with age. This degradation in aging populations results in inadequate immune responses to invading pathogens, self-antigens, undesirable and malfunctioning cells, and even to vaccines. “Furthermore, the aged immune system elicits an inadequate response to vaccines, leaving the elderly susceptible to pathogens despite being vaccinated against them. This is especially poignant in the wake of an ongoing pandemic where the mortality rate is disproportionately high in the elderly.” Researchers from the University of Florida authored a well-written review article (with exceptionally vivid figures and illustrations) exploring a potential cause of the aging immune system. They believe therapies that could target this cause may stave off age-related diseases and improve our quality of life as we age. The paper was published by Aging (Aging-US) in 2021, and entitled, “Cellular senescence in lymphoid organs and immunosenescence.” Full blog - https://www.impactjournals.com/journals/blog/aging/%e2%80%8b%e2%80%8bimmunosenescence-and-the-aging-immune-system/ Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.203405 DOI - https://doi.org/10.18632/aging.203405 Full text - https://www.aging-us.com/article/203405/text Correspondence to: Daohong Zhou email: zhoudaohong@cop.ufl.edu Keywords: cellular senescence, immunosenescence, immune senescence, senescence associated secretory phenotype (SASP), thymus 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 http://www.Aging-US.com​​ or connect with us on: Twitter - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ SoundCloud - https://soundcloud.com/aging-us​ YouTube - https://www.youtube.com/agingus​ LinkedIn - https://www.linkedin.com/company/aging​ Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com​​ or connect with @ImpactJrnls Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Aging-US
Aging-US: A Model of the Aged Lung Epithelium in Idiopathic Pulmonary Fibrosis

Aging-US

Play Episode Listen Later Aug 30, 2021 2:51


Aging-US published "A model of the aged lung epithelium in idiopathic pulmonary fibrosis" which reported that Iiopathic pulmonary fibrosis (IPF) is an age-related disorder that carries a universally poor prognosis. By exposing mouse alveolar epithelial cells to repeated, low doses of bleomycin, instead of usual one-time exposures, the authors uncovered changes strikingly similar to those in the IPF lung epithelium. They propose that this simple yet powerful tool could help uncover new biological mechanisms and assist in developing new pharmacological tools to treat the disease. Dr. Ross Summer from The Jane and Leonard Korman Respiratory Institute as well as Dr. Freddy Romero from The Baylor College of Medicine said, "Idiopathic pulmonary fibrosis (IPF) represents one of the most aggressive and irreversible lung diseases, has an unknown etiology, and limited therapeutic options." IPF arises from low-grade insults to the alveolar epithelium, which exhaust stem cell capacity and activate pathways that result in progressive tissue remodeling. Age represents the most significant risk factor for the development of IPF. Senescent cells are believed to drive immune cell and fibroblast activation via their production of secretory proteins (SASP), such as IL-6, TNF-β and TGF-β. Emerging evidence indicates that experimentally-induced pulmonary fibrosis can be ameliorated by targeting senescent cells for destruction [15]. This suggests a role for senolytic therapies in the treatment of IPf. The Summer/Romero Research Team concluded in their Aging-US Research Output, "we describe a novel model of the IPF lung epithelium that displays many characteristics of the dysfunctional IPF alveolar epithelium. Given its low cost and ease of implementation, we believe our model is ideally suited for uncovering the molecular underpinnings driving mitochondrial dysfunction, cellular senescence and loss of proteostasis in IPF. Further, we believe our model is also ideally suited for high throughput testing of novel pharmacological compounds directed at the alveolar epithelium. This includes drugs aimed at eliminating dysfunction epithelial cells, such as senolytic medications and agents that aim to restore health to the IPF alveolar epithelium" DOI - https://doi.org/10.18632/aging.203291 Full Text - https://www.aging-us.com/article/203291/text Correspondence to: Ross Summer email: Ross.Summer@Jefferson.edu and Freddy Romero email: Freddy.RomeroVasquez@bcm.edu Keywords: aging, IPF, mitochondria, proteostasis, epithelial cells About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways. To learn more about Aging-US, please visit http://www.Aging-US.com or connect with @AgingJrnl Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact 18009220957x105 MEDIA@IMPACTJOURNALS.COM

SSSF Rangetime
2021 Nationals Podcast Series: Beretta Pro, JJ Racaza

SSSF Rangetime

Play Episode Listen Later Jul 13, 2021 9:29


On day 6 of Nationals, presented by Beretta, we sit down with pro shooter, JJ Racaza to recap his time spent with SASP athletes at their National Championship.

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SASP Ep6 - Wolf 359 and A Girl Like Her

Share A Story

Play Episode Listen Later Jun 21, 2020 99:08


Hello Dear Listener, This is Darian. In this episode, I shared a story from another podcast called Wolf 359. There is some truly fantastic work that has gone into it. This leads to a discussion about someone's worth even if they have caused irreparable harm in the past. Laureen talks about a movie called A Girl Like Her. It is about a bully who goes through the painful process of realizing she is a bully. I also share my past experience with the topic. We would like to express our grief and sadness about George Floyd's tragic murder at the hands of police officers. We recorded this episode before his death so we don't talk about it. But the ideas we talk about - redemption and worth after a tragedy, along with bullying in ignorance - can certainly help us as we try to learn lessons, heal, and correct the broken parts of our society. Murder is always disturbing. But there is something especially disturbing when it is committed by someone to whom we entrust with great authority. This has shined a spotlight on a very ugly reality that many people are forced to live every day. I truly believe that stories define who we are. We all have toxic stories in our heads and hearts that can cause us to jump to very wrong and very bad conclusions that hurt people. To rid ourselves of these toxins, I've found that one of the best antidotes is good stories. This is your first homework assignment: Get to know someone that looks different than you. Preferably, this is someone that will be a little scary to you. Ask him or her to share a story that is meaningful. Then go to shareastory.fm/MyNewFriendsStory and share that story with us as a comment. Also, share what you learned about this person. What did you think about them that wasn't true? We want to know about your experience! We will share some of your comments on future episodes.

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SASP Ep5 - Peder and the Water Sprite

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Play Episode Listen Later May 10, 2020 59:39


Hello Dear Listener, This is Darian writing right now. When Laureen and I decided to start this podcast, we wanted it to mainly be us talking with each other but we also wanted to have some guests on as well. This episode is the first one where we have a guest storyteller. Her name is Rachel Hedman. She loves stories so much that she founded an organization just for telling stories. It is called Story Crossroads. We both hope you and your loved ones are staying safe! Here are some of the things we talk about in the episode: Rachel Hedman Story Crossroads Spectacular Free Trial at Audible Patreon stories@shareastory.fm Facebook Instagram Twitter

water sprite peder sasp hello dear listener
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SASP Ep4 - Field of Dreams

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Play Episode Listen Later May 3, 2020 33:15


Hello Dear Listener, Darian here. Today, you get the second part of a conversation the two of us started last episode with Laureen telling me all about Jane Eyre. Now it is my turn to talk about that old Kevin Costner movie, Field of Dreams. We also have a new sponsor for the show. That sponsor is Audible. If you listen to a lot of spoken audio, Audible would be worth looking in to. Go to audibletrial.com/shareastory to get a free audiobook and some free Audible original titles. When you do, it will help us out too. Laureen and I have been using Audible for years and they have been very kind to us. We feel very good recommending them :) If you want to support the show or join our exclusive community of storytellers, go to Patreon.com/shareastory to sign up there. We love our patrons and we thank you for your generosity! Are you stuck inside right now? Stuck outside? Or somewhere in between? Tell us about it! We would love to hear your stories. Here is how: shareastory.fm/contact stories@shareastory.fm Facebook Instagram Twitter Patreon We hope you and your loved ones are staying safe and in good spirits. We can get through these very unusual times! Thanks for listening, Darian Oliphant