Longevity Papers Podcast

Longevity Papers
  • 0.0 (0)
  • TECHNOLOGY
  • UPDATED WEEKLY

The Longevity Papers podcast focuses on the latest research papers in longevity biotech. Each episode covers a few of the tens of papers in https://longevitypapers.com, which finds the latest interesting papers with longevity focus from preprint servers.

  1. 12/14/2025

    Longevity Papers 2025-12-14

    A Fourfold Male-Specific Lifespan Extension via Canonical Insulin/IGF-1 Signaling (Russell et al., University of Alabama at Birmingham, December 5, 2025, BioRxiv, https://www.biorxiv.org/content/10.64898/2025.12.02.691904v1 ) - We explore how the daf-2 mutation extends male C. elegans lifespan by an extraordinary 4-fold with preserved healthspan, establishing sex as a primary determinant of longevity potential rather than a secondary variable. This challenges our understanding of insulin/IGF-1 signaling and suggests sex-specific interventions may be critical for anti-aging therapeutics. 2) Lifespan-extending downregulation of insulin signaling reduces germline mutation load (Duxbury et al., University of East Anglia, December 5, 2025, BioRxiv, https://www.biorxiv.org/content/10.64898/2025.12.05.692572v1 ) - We examine how reducing insulin/IGF-1 signaling in adulthood simultaneously extends somatic lifespan and reduces germline mutation rates by ~50 percent, dissolving the classical reproductive-somatic trade-off. The HRDE-1 epigenetic silencing pathway emerges as a novel mechanism linking nutrient sensing to genome stability across generations. 3) A Global Metabolomic and Lipidomic Landscape of Human Plasma Across the Lifespan (Liu et al., University of Science and Technology of China, December 6, 2025, Aging Cell, https://pubmed.ncbi.nlm.nih.gov/41351469/ ) - We discuss how untargeted metabolomics of 136 individuals reveals nonlinear metabolic trajectories with critical transition points, elevated amino acids and lipid dysbalance characterizing aging, and development of a clinically applicable plasma metabolite-based aging clock that may outperform epigenetic clocks for mortality prediction. 4) Genome-wide association study of proteomic aging reveals shared genetic architectures with longevity, early life development, and age-related diseases (Argentieri et al., Massachusetts General Hospital, December 4, 2025, MedRxiv, https://www.medrxiv.org/content/10.64898/2025.12.03.25341518v1 ) - We analyze 27 genetic loci associated with proteomic age gap showing strong genetic correlation with longevity (r=-0.83), with validated polygenic scores predicting increased odds of exceptional longevity and mechanistic links to FTO and m6A methylation-regulated metabolic aging. 5) Gut metabolism links precision nutrition, exercise, and healthspan in Drosophila melanogaster

    35 min

  2. 11/30/2025

    AI, Splicing, and Nuclear Tension: 4 New Papers on Aging

    In this episode, we analyze four standout papers from longevity research (November 17–30, 2025). The sources indicate that none achieve the paradigm-shifting breakthrough required for decades-long (10+ year) human lifespan extension. 1. Targeting Nuclear Tension to Rejuvenate Blood (Paper #74) Title: Targeting RhoA nuclear mechanoactivity rejuvenates aged hematopoietic stem cells Authors: Eva Mejía-Ramírez, Pablo Iáñez Picazo, Barbara Walter, et al. Source/Date: Nature Aging, November 25, 2025 URL: https://pubmed.ncbi.nlm.nih.gov/41286... This paper identifies a genuinely novel mechanotransduction axis (NE tension → P-cPLA2 → RhoA) in aging hematopoietic stem cells (HSCs). Aged HSCs accumulate pathological nuclear envelope (NE) tension, which hyperactivates RhoA signaling, leading to loss of youthful H3K9me2 heterochromatin and de-repression of retrotransposons. RhoA inhibition pharmacologically restores NE homeostasis, recovers H3K9me2, and improves HSC regenerative capacity and lymphomyeloid balance in vivo. This work is strong mechanistic discovery, but the effects are HSC-specific. Systemic longevity impact is limited, potentially leading to 2–4 year healthspan gains in immune resilience in highly optimized scenarios, falling short of transformative longevity goals. 2. AI Agents for Intervention Discovery (Paper #41) Title: Autonomous AI Agents Discover Aging Interventions from Millions of Molecular Profiles Authors: Ying, K., Tyshkovskiy, A., Moldakozhayev, A., et al. Source/Date: BioRxiv, November 20, 2025 URL: https://www.biorxiv.org/content/10.11... This research uses the ClockBase Agent to autonomously reanalyze 43,602 intervention-control comparisons across multiple aging clocks. It identified over 500 interventions that reduce biological age, including ouabain. Experimental validation showed ouabain reduced frailty, decreased neuroinflammation, and improved cardiac function in aged mice. This represents genuine methodological novelty in mining existing biomedical data for aging interventions, but the intervention (ouabain) is a known cardiac glycoside, and the effects are considered modest. 3. Splicing Dysregulation in Muscle Aging (Paper #22) Title: TGFβ-Smad3 signaling restores cell-autonomous Srsf1-mediated splicing of fibronectin in aged skeletal muscle stem cells Authors: Yuguo Liu, Svenja C Schüler, Simon Dumontier, et al. Source/Date: Nature Communications, November 22, 2025 URL: https://pubmed.ncbi.nlm.nih.gov/41271... This paper maps the TGFβ1-Smad3-Srsf1-EDB(+)FN pathway linking RNA splicing dysregulation to muscle regenerative failure in aging. TGFβ1 activation restored fibronectin splicing and improved muscle repair in aged mice during a defined regeneration interval. This is solid mechanistic work aligning with RNA splicing being an emerging core aging axis. However, the therapeutic window appears narrow, confined to acute regeneration intervals, and lacks whole-organism lifespan data. 4. The Nonhuman Primate Aging Atlas (Paper #70) Title: A multi-omics molecular landscape of 30 tissues in aging female rhesus macaques Authors: Gong-Hua Li, Xiang-Qing Zhu, Fu-Hui Xiao, et al. Source/Date: Nature Methods, November 18, 2025 URL: https://pubmed.ncbi.nlm.nih.gov/41249... This is the first comprehensive multi-omics atlas across 30 tissues in nonhuman primates. The key finding is that tissue aging is asynchronous and stratified by mRNA translation efficiency; tissues with declining translational capacity exhibit accelerated aging and drive whole-body aging. This paper links translational capacity to tissue-specific aging rates but is primarily descriptive, providing an excellent resource rather than interventional proof of lifespan extension. Overall Assessment: This body of work is valuable for resource building and hypothesis generation, focusing on incremental improvements across areas like mechanotransduction, translational capacity, and AI methodology. However, none provide the clear therapeutic path or fundamental aging reversal mechanism necessary to achieve breakthroughs targeting decades-long human lifespan extension. This podcast is AI generated and may contain errors.

    24 min

  3. 11/14/2025

    Longevity Papers 2025-11-14

    In this episode of Longevity Papers, we critically analyze the five most impactful papers from this week (November 10-14, 2025) selected from longevitypapers.com for biotech researchers and longevity enthusiasts. 1) 'circHERC1-A telomerase activator' (Yumeng Cui et al., Beijing Institute of Biotechnology, November 12, 2025, Science Advances, https://pubmed.ncbi.nlm.nih.gov/41223261/ ) - We explore how the circular RNA circHERC1 activates telomerase expression by recruiting RNA Pol II to the TERT promoter. Notably, circHERC1 declines with age, correlating with reduced telomerase activity. Restoration via AAV or extracellular vesicles enhances telomere elongation and reverses aging phenotypes including improved cognition and physical performance. This addresses telomere attrition as a hallmark of aging, building on decades of telomerase biology since Greider/Blackburn 1985, with a unique endogenous regulatory mechanism distinct from previous failed small-molecule approaches. 2) 'HDAC2 inhibition restores H4K16 Acetylation and Rescues Cellular Senescence in Hutchinson-Gilford progeria syndrome' (Karimpour et al., University of Alberta, November 7, 2025, BioRxiv, https://www.biorxiv.org/content/10.1101/2025.11.07.687234v1 ) - We examine how systematic screening identified HDAC2 (not SIRT1) as the dominant deacetylase responsible for H4K16ac loss in accelerated aging. Pharmacological HDAC2 inhibition restores H4K16 acetylation, rescuing nuclear morphology, proliferative capacity, and reducing senescence in HGPS cells. This represents a specificity win over pan-HDAC inhibitors that failed clinically, with potential transformative implications if HGPS lifespan is extended, proving concept for broader aging populations. 3) 'Targeting Endothelial KDM5A to Attenuate Aging and Ameliorate Age-Associated Metabolic Abnormalities' (Rifeng Gao et al., Zhejiang University, November 14, 2025, Advanced Science, https://pubmed.ncbi.nlm.nih.gov/41236095/ ) - We discuss how endothelial-specific KDM5A deficiency causes shortened lifespan with senescent phenotypes (fat accumulation, reduced thermogenesis, kyphosis), demonstrating causative endothelial aging. The mechanism links epigenetics to metabolism: KDM5A regulates H3K4me3 at FABP4 promoters. Maintaining VEC-specific KDM5A prolongs lifespan, establishing the KDM5A/FABP4 axis as a therapeutic target for vascular aging and systemic metabolic dysfunction. 4) 'Mitochondrial dysfunction drives age-related degeneration of the thoracic aorta' (Arjune S Dhanekula et al., University of Washington, November 14, 2025, GeroScience, https://pubmed.ncbi.nlm.nih.gov/41233677/ ) - We analyze how elamipretide (SS-31), a mitochondria-targeted peptide in clinical trials, restores Complex II respiration to young levels in aged aortas, reducing stiffness, elastin breaks, and inflammatory MMP9 expression. This demonstrates causation via pharmacological rescue of a hallmark aging process, with SS-31 already being tested in Friedreich's ataxia and heart failure—this aging application would expand clinical relevance significantly. 5) 'Defining Microbiota-Derived Metabolite Butyrate as a Senomorphic: Therapeutic Potential in the Age-Related T Cell Senescence' (Nia Paddison Rees et al., University of Birmingham, November 7, 2025, Aging Cell, https://pubmed.ncbi.nlm.nih.gov/41201238/ ) - We examine butyrate as a senomorphic agent preventing senescence accumulation rather than eliminating it. The mechanism: butyrate suppresses IL-6/IL-8 SASP secretion via mTOR/NF-κB inhibition, with reduced DNA damage markers and mitochondrial ROS. Young fecal microbiota reverse aged splenic senescence in vivo, implicating the microbiota-immune axis. Butyrate is dietary, cheap (0/month), and represents a scalable intervention if lifespan studies confirm efficacy. This podcast is AI generated and may contain errors.

    13 min

  4. 11/02/2025

    Longevity Papers 2025-11-02

    In this episode of Longevity Papers podcast, we discuss three cutting-edge papers on aging mechanisms and potential interventions, featured this week on longevitypapers.com. 1) Decay in transcriptional information flow is a hallmark of cellular aging (Emison et al., Yale University, October 30, 2025, biorxiv, https://www.biorxiv.org/content/10.1101/2025.10.30.685689v1 ) - We explore a novel information-theoretic framework showing that aging is fundamentally a loss of coordinated transcription factor activity across networks. The authors use single-cell RNA-seq across ten tissues to show mutual information between transcription factors and target genes declines with age, but crucially, in silico upregulation of key transcription factors restores youthful gene expression patterns. This offers a systems-level understanding of aging and suggests targeted transcription factor reinforcement as a rejuvenation strategy. 2) FOXM1 enhances DNA repair in aged cells to maintain the peripheral heterochromatin barrier to senescence enhancers (Sousa-Soares et al., Universidade do Porto, October 30, 2025, biorxiv, https://www.biorxiv.org/content/10.1101/2025.10.29.685369v1 ) - We examine a powerful age-reversal mechanism where FOXM1 induction restores epigenetic integrity in aged cells. The pathway is elegant: FOXM1 drives DNA repair genes, preserves the G9a methyltransferase, maintains H3K9me2 heterochromatin at the nuclear periphery, and thereby silences senescence-enhancer landscapes. This work identifies FOXM1 as a potential age-reversal factor rather than merely slowing decline. 3) Lactobacillus Salivarius-Derived Indole-3-Acetic Acid Promotes AHR-PARP1 Axis-Mediated DNA Repair to Mitigate Intestinal Aging (Cao et al., Chinese Academy of Sciences, October 28, 2025, Advanced Science, https://pubmed.ncbi.nlm.nih.gov/41147383/ ) - We discuss a concrete, translatable microbiota-to-DNA repair axis where bacterial indole-3-acetic acid activates the aryl hydrocarbon receptor, which potentiates PARP1 activity to enhance DNA repair in intestinal epithelial cells. This identifies Lactobacillus salivarius as a candidate probiotic intervention and offers a direct path to clinical trials. Together, these papers represent some of the strongest mechanistic work on aging this week, combining systems biology, epigenetics, and microbiome approaches. This podcast is AI generated and may contain errors.

    15 min

  5. 10/19/2025

    Longevity Papers 2025-10-19

    In this episode of Longevity Papers, we critically analyze five research papers from the week of October 13-19, 2025, curated from longevitypapers.com: 1) Mutation-Agnostic Base Editing of the Progerin Farnesylation Site Rescues Hutchinson-Gilford Progeria Syndrome Phenotypes in Neuromuscular Organoids (Kim et al., Seoul National University, October 16, 2025, bioRxiv, https://www.biorxiv.org/content/10.1101/2025.10.16.682736v1 ) - We examine the FATE platform for treating progeria through mutation-agnostic base editing, discussing its potential and significant translation challenges including organoid model limitations and in vivo delivery obstacles. 2) Phenome-Wide Multi-Omics Integration Uncovers Distinct Archetypes of Human Aging (Li et al., October 14, 2025, arXiv, http://arxiv.org/abs/2510.12384v1 ) - We critically evaluate claims of distinct aging subtypes from multi-omics data, addressing concerns about false discovery rates and the fundamental challenge of distinguishing signal from noise in high-dimensional biological data. 3) A Population-scale Single-cell Spatial Transcriptomic Atlas of the Human Cortex (Han et al., Lingang Laboratory Shanghai, October 14, 2025, bioRxiv, https://www.biorxiv.org/content/10.1101/2025.10.13.681959v1 ) - We discuss this comprehensive brain atlas showing age-related neuronal vulnerability and glial activation, while noting its limitations as an observational study that cannot distinguish cause from consequence. 4) Chaperone-mediated autophagy regulates neuronal activity by sex-specific remodelling of the synaptic proteome (Khawaja et al., Albert Einstein College of Medicine, October 15, 2025, Nature Cell Biology, https://pubmed.ncbi.nlm.nih.gov/41087566/ ) - We explore how CMA activation restores synaptic function in aging models, highlighting the sex-specific effects and therapeutic potential while discussing translation challenges. 5) Accelerated Regeneration of Senescent Bone Injury through Age- and Sex-Independent Macrophage Polarization (Fukuda et al., Tokushima University, October 15, 2025, ACS Applied Materials and Interfaces, https://pubmed.ncbi.nlm.nih.gov/41091908/ ) - We examine phosphatidylserine liposomes for bone repair in aging, noting the age/sex-independent macrophage effects while questioning the broader applicability beyond orthopedic applications. We provide critical analysis of statistical limitations, experimental needs, and the reality that this represents a typical week where 95 percent of research is incremental rather than transformative for longevity biotech. This podcast is AI generated and may contain errors.

    32 min

  6. 09/19/2025

    Longevity Papers 2025-09-19

    In this episode of Longevity Papers, we critically analyze the week of September 15-19, 2025 papers from longevitypapers.com for biotech researchers. We examine five papers: 1) The DREAM Complex Links Somatic Mutation, Lifespan, and Disease (Koch et al., UC San Diego, September 18, 2025, bioRxiv, https://www.biorxiv.org/content/10.1101/2025.09.15.676396v1 ) - We discuss how DREAM complex repression affects DNA repair and lifespan across 92 mammalian species, but question whether the modest 4.2% mutation reduction will translate to meaningful longevity gains. 2) Nucleosome Stability Safeguards Cell Identity, Stress Resilience and Healthy Aging (Tanaka et al., Sanford Burnham Prebys, September 18, 2025, bioRxiv, https://www.biorxiv.org/content/10.1101/2025.09.17.676776v1 ) - We explore cross-species evidence that nucleosome stability preserves cellular function, while noting the gap between artificial histone mutants and actionable interventions. 3) Estimating Universal Mammalian Lifespan via Age-Associated Epigenetic Entropy (Alba-Linares et al., CINN-CSIC, September 17, 2025, bioRxiv, https://www.biorxiv.org/content/10.1101/2024.09.06.611669v2 ) - We examine claims of a universal 220-year maximum mammalian lifespan based on epigenetic entropy patterns and discuss why correlation may not equal causation. 4) Metabolomic Signatures of Extreme Old Age from the New England Centenarian Study (Monti et al., Boston University, September 16, 2025, bioRxiv, https://www.biorxiv.org/content/10.1101/2025.09.10.675341v1 ) - We analyze bile acid elevation in centenarians while addressing survivor bias limitations in extreme longevity studies. 5) Guided Multi-Agent AI Invents Transcriptomic Aging Clocks (Agarwal et al., MIT, September 12, 2025, bioRxiv, https://www.biorxiv.org/content/10.1101/2025.09.08.674588v1 ) - We review this computational advance in aging clock accuracy while emphasizing that better measurement tools dont automatically translate to longevity breakthroughs. Throughout, we maintain skeptical analysis of whether these incremental findings will lead to the 10-year-plus lifespan extensions that longevity biotech truly needs. This podcast is AI generated and may contain errors.

    36 min

  7. 09/11/2025

    Longevity Papers 2025-09-12

    This week on Longevity Papers, we didn't find so many interesting papers so we go back to a classic research by Cynthia Kenyon, but also analyze recent research from longevitypapers.com 1) The first long-lived mutants: discovery of the insulin/IGF-1 pathway for ageing. (Kenyon, Cynthia 12 January 2011 , Phil. Trans. R. Soc. B3669–16 https://doi.org/10.1098/rstb.2010.0276 ) 2) The aging factor EPS8 induces disease-related protein aggregation through RAC signaling hyperactivation (Koyuncu et al., University Hospital Cologne, Sept 4, 2025, https://pubmed.ncbi.nlm.nih.gov/40903652/ ) - Identifies EPS8 as a convergent aging factor promoting protein aggregation across multiple neurodegenerative diseases, with USP4 as a potential therapeutic target. 3) Platelet Factor 4 (PF4) Regulates Hematopoietic Stem Cell Aging (Zhang et al., University of Illinois Chicago, Sept 8, 2025, https://pubmed.ncbi.nlm.nih.gov/40920871/ ) - Demonstrates actual rejuvenation of aged hematopoietic stem cells through PF4 signaling, though systemic safety and lifespan effects remain to be proven. We discuss why most papers this week represent incremental progress rather than paradigm shifts, the challenges of translating promising mouse studies to humans, and what experiments are needed to validate these findings for meaningful life extension. This podcast is AI generated and may contain errors.

    46 min

  8. 09/02/2025

    Longevity Papers 2025-09-02

    In this episode of Longevity Papers, we critically analyze recent research with appropriate skepticism for biotech researchers and longevity enthusiasts. First we discuss the ARDD conference that took last week in Copenhagen, including a replacement panel, and a related paper from Nature Aging back in May 2025: Replacement as an aging intervention (Sierra Lore et al., The Buck Institute, https://www.nature.com/articles/s43587-025-00858-6 ). Featured from longevitypapers.com: 1) Reprogramming Factors Activate a Non-Canonical Oxidative Resilience Pathway That Can Rejuvenate RPEs and Restore Vision (Lu et al., Whitehead Institute, September 01, 2025, bioRxiv, https://www.biorxiv.org/content/10.1101/2025.08.30.673239v1 ) - We examine claims that Yamanaka factors restore vision through GSTA4-mediated pathways, discussing why vision restoration studies require extreme caution and what validation experiments are needed. 2) Multi-modal atlas of lifestyle interventions reveals malleability of ageing-linked molecular features (Herzog et al., University of Innsbruck, September 01, 2025, bioRxiv, https://www.biorxiv.org/content/10.1101/2025.08.30.673115v1 ) - We analyze this comprehensive multi-omics study claiming intermittent fasting shows age-opposing molecular changes, explaining why 6-month biomarker studies rarely translate to meaningful longevity gains. 3) Avoidance Of Rejuvenation: A Stress Test For Evolutionary Theories Of Aging (Aisin et al., City University of Hong Kong, August 28, 2025, bioRxiv, https://www.biorxiv.org/content/10.1101/2025.08.24.671987v1 ) - We discuss this theoretical framework questioning why rejuvenation is rare in nature and whether this constrains intervention possibilities. As typical for most weeks, these papers represent incremental advances rather than paradigm shifts, with significant methodological limitations that require careful interpretation before any clinical applications. This podcast is AI generated and may contain errors.

    54 min
See All (35)

About

The Longevity Papers podcast focuses on the latest research papers in longevity biotech. Each episode covers a few of the tens of papers in https://longevitypapers.com, which finds the latest interesting papers with longevity focus from preprint servers.

Information