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Translating Aging: Daily Summaries Delivered
by BioAge Labs
On Translating Aging, we talk with the worldwide community of researchers, entrepreneurs, and investors who are moving longevity science from the lab to the clinic. We bring you a commanding view of the entire field, in the words of the people and companies who are moving it forward today. The podcast is sponsored by BioAge labs, a clinical-stage biotechnology company developing therapies to extend human healthspan by targeting the molecular causes of aging.
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- Jun 17, 202640 min
A Promise Kept — Phase 1 Data for a 7-KC-Clearing Drug (Oki O'Connor, Cyclarity Tx)
Matthew "Oki" O'Connor is the CEO of Scientific Affairs at Cyclarity Therapeutics, a clinical-stage biotech building a new class of medicines designed not to slow the accumulation of vascular damage but to reverse it. Oki and Chris first crossed paths as postdocs at Lawrence Berkeley National Lab in the mid-2000s — Oki was in Irina Conboy's lab, not far from the late Judy Campisi's group, where Chris was then working on cellular senescence. After Berkeley, Oki spent nearly a decade running the research program at the SENS Research Foundation, the organization most identified with the "damage repair" framing of aging biology, before co-founding Cyclarity (then known as Underdog Pharmaceuticals) in 2019 to translate one of SENS's most drug-tractable ideas into an actual molecule.When Oki was last on the show in March of 2023 (Episode 36), Cyclarity was deep in IND-enabling work and its lead asset, UDP-003, had only ever seen the inside of a mouse artery. At the end of that conversation, Chris asked what Oki hoped to be discussing the next time he visited. He answered, bluntly, that he wanted to be presenting human data. Last month, at the AHA Vascular Discovery Sessions, Cyclarity reported the results of their first-in-human Phase 1 trial of UDP-003 — a designed cyclodextrin that selectively binds 7-ketocholesterol, the oxidized cholesterol species that drives foam cell formation and arterial plaque. He's back to discuss what the drug actually did when it went hunting for 7KC inside a living human being.In this episode, Chris and Oki cover the unmet need that lipid-lowering drugs — statins, PCSK9 inhibitors, the coming Lp(a) agents — still don't address: none of them remove the damage already sitting in an artery wall. Oki explains the basic chemistry of 7-ketocholesterol and why macrophages, lacking the machinery to recycle it, collapse into foam cells and seed the necrotic core of advanced plaque. They walk through the engineering of UDP-003 as a dimeric beta-cyclodextrin "double cone" tuned for a single oxidized cholesterol species, the design of the 72-volunteer Australian Phase 1, and the exploratory pharmacodynamic readout that has the field's attention: dose-dependent urinary excretion of 7KC, stoichiometric with drug, cleared within a day. The conversation then turns to the 150-patient Phase 2 plan in coronary artery disease patients with plaque imaging as the primary biological readout, the funding math that stands between Cyclarity and that trial, the platform's reach into NASH, vascular dementia, AMD, and aging itself, and how all of this descends from the SENS damage-repair philosophy that Oki has been carrying since LBL.The Finer Details:- Why current standard of care is not enough — statins, PCSK9 inhibitors, GLP-1s, and the soon-to-arrive Lp(a) lowering agents all act by slowing the accumulation of arterial damage, not by reversing what's already there; despite 30 years on the market, statins have never demonstrated an all-cause mortality benefit in a clinical trial, and even the best statin imaging data shows only 1–2% plaque volume regression at very high doses in a subset of patients- The scale of the problem — atherosclerosis is estimated to contribute to roughly 40% of all human deaths once heart attack, stroke, and a surprisingly large COPD contribution are risk-adjusted in, on top of an enormous morbidity tail that includes angina, peripheral artery disease (up to and including amputation), and a growing case for vascular dementia as an undercounted driver of cognitive decline- The biology of 7-ketocholesterol — when an oxygen free radical reacts with cholesterol, it preferentially attacks the 7 position, and a second oxidation step locks the molecule into 7KC, a stable toxic species cells were essentially never equipped to recycle; it builds up in long-lived cells like macrophages, eventually shutting down their ability to traffic lipids back to the liver via HDL and converting them into foam cells that seed soft plaque and, over years, the necrotic core of advanced lesions- The molecular design of UDP-003 — cyclodextrins are naturally occurring carbohydrate rings; the beta size fits half a cholesterol molecule, and Cyclarity's in silico work showed that two beta-cyclodextrins facing wide-side to wide-side form a "double cone" that can fully encapsulate a single cholesterol; engineered correctly, that wrapper can be made selective for 7KC over native membrane cholesterol, which is what gives the drug its therapeutic window- The Phase 1 trial design and result — a traditional 72-volunteer safety study in Australia, split between single ascending dose and multiple ascending dose arms, escalating up to six doses at what Cyclarity believes will be the efficacious level; no serious adverse events, no bioaccumulation, drug excreted essentially completely in the urine (as predicted preclinically), and — the headline ex
- May 20, 202646 min
Beyond senolytics: senoadaptive drugs & clinical data on GPX4 modulation (Dr. Marco Quarta, Rubedo)
Marco Quarta is co-founder and Chief Scientific Officer of Rubedo Life Sciences, a precision-therapeutics company developing medicines that target the pathological cell states that drive age-associated disease. Marco's first appearance on the show was three years ago, in February 2023 (Episode 35), when Rubedo was a much earlier-stage company committed to the then-contrarian premise that "the senescent cell" is not a single entity but a heterogeneous family of cell states that needs to be deconvoluted at the single-cell level. In March 2026, Rubedo reported preliminary Phase 1b/2a clinical data for its lead candidate, RLS-1496, a first-in-class topical GPX4 modulator. Marco returns to the show to discuss what survived contact with human biology.In this episode, Chris and Marco unpack the readout from Rubedo's basket trial across four skin indications — psoriasis, atopic dermatitis, actinic keratosis, and photoaged skin — and the biology that underlies it. RLS-1496 came clean on safety in all four indications, with significant efficacy signals despite small patient numbers and short (20–30 day) treatment courses. More provocatively, the clinical and translational data have pushed Marco to redefine what kind of drug this actually is. Rather than a next-generation senolytic, GPX4 modulation appears to act as a state-gating intervention: it triggers ferroptosis in deeply senescent cells that have already crossed a redox threshold, while inducing a hormetic "redox reset" in stressed-but-recoverable cells that restores them to a healthier state. Marco proposes a new category to capture this dual action — adaptive senotherapeutics, or senoadaptive drugs — distinct from senolytics and senomorphics.The conversation traces the arc from Rubedo's founding thesis to a clinically validated platform (ALEMBIC, the AI-enabled single-cell multiomics engine that surfaced GPX4 as a target), through the strategic logic of leading with skin, into the broader question every longevity-biotech founder eventually has to answer: when does a disease-by-disease franchise become a credible preventive geroscience platform? Marco lays out the GLP-1 analogy explicitly — an anchor indication and a label-expansion roadmap that could carry GPX4 modulation from dermatology into respiratory, neurodegenerative, and metabolic disease, and ultimately into the use case where biomarkers of cellular senescence flag patients for therapy decades before disease becomes clinically apparent.The Finer Details:How Marco's 2023 contrarian view — that "senescent cells" hide a tissue- and state-specific reality — has been reinforced by the clinic, and how Rubedo's framing has shifted from "targeting senescent cells" to "targeting pathological cell states"The biology of GPX4 as a lipid-peroxidation gatekeeper, why senescent cells have intrinsic vulnerabilities (p16, p21, CDK4/6 inhibition) that make them ferroptosis-sensitive, and how Rubedo's approach differs from oncology-focused GPX4 programs at Takeda and othersThe "senoadaptive" mechanism — RLS-1496 eliminates GPX4-dependent senescent cells via ferroptosis while triggering NRF2/Keap1-driven redox reset, autophagy, and epigenetic remodeling in recoverable cells, restoring tissue trajectory from degenerative to regenerativeWhy Rubedo led with skin: clean regulatory path, accessible tissue, the ability to read out aging biology anddisease in the same trial, and a label-expansion runway into systemic indicationsPhase 1b (Europe) and Phase 2a (US) basket-trial results across psoriasis, atopic dermatitis, photoaged skin, and actinic keratosis: clean safety in 4/4 indications and significant efficacy signals — itch reduction in atopic dermatitis, decreased lesional thickness in psoriasis, target-engagement-correlated clinical improvement in photoaged skinThe richness of the translational dataset: biopsies, tape-stripping, spatial transcriptomics, proteomics, multiplex histomics, plasma biomarkers — all feeding back into ALEMBIC to refine the platformWhy actinic keratosis is the most strategically important indication — an age-related, chronic-inflammatory, precancerous condition where Rubedo can simultaneously test disease modification and biological-age reversalThe Rubedo–Beiersdorf partnership and the cosmetic vertical as a parallel commercial axisPipeline beyond skin: targeting aberrant basaloid stem cells in IPF and other pulmonary indications using different modalities (prodrugs, PROTACs, ADCs) to achieve cell-state selectivityThe longer-arc vision: senescence biomarkers as a "prediabetes-style" early signal, with senoadaptive drugs deployed decades before disease — and what a GLP-1-scale franchise might look like for GPX4 modulationQuotes:"There is not such a thing as a senescent cell — like there is not a c
- Aug 13, 202551 min
Investing in the Future of Longevity (Sergey Jakimov, Managing Partner, LongeVC)
Sergey Jakimov is the Managing Partner and co-founder of LongeVC, one of Europe's most active longevity-focused venture capital firms, currently raising its second fund targeting $250 million.In this episode, Chris and Sergey explore the investment landscape shaping longevity biotechnology today. They discuss LongeVC's pragmatic approach to longevity investing—focusing on disease-modifying therapies rather than targeting aging itself—and why this strategy has been successful across their portfolio. Sergey shares insights from major successes including Rubedo's partnership with Beiersdorf and Turn Bio's deal with HanAll, explaining what these deals signal about pharma's evolving interest in longevity approaches. The conversation covers critical topics for researchers and entrepreneurs: common pitfalls in academic spin-offs, the importance of clear regulatory pathways, and how the upcoming patent cliff is creating new opportunities for early-stage biotechs in the longevity space.Listeners will gain valuable insights into what makes a longevity company investable, how to navigate the transition from academic research to commercial venture, and why solving age-related diseases one by one may ultimately lead to a holistic understanding of aging itself.The Finer Details:Sergey's journey from aspiring neurosurgeon to deep tech entrepreneur to longevity investorLongeVC's pragmatic philosophy: targeting specific diseases rather than aging as a wholeThe convergence of biotech, regenerative medicine, and AI in the longevity spaceKey criteria for early-stage investment: disease indication, balanced teams, clean IP transferWhy "five scientists in a room" and "great mouse data" don't make an investable companyThe importance of platforms having their own pipelines, not just service modelsHow LongeVC's scientific advisory board (including Alex Zhavoronkov, Vadim Gladyshev, Thomas Rando) evaluates investmentsSuccess stories: Rubedo's senolytic partnership and Turn Bio's epigenetic reprogramming dealThe changing dynamics between pharma and biotech driven by patent cliffs and urgency to find the "next GLP-1"Regulatory strategies: focusing on specific endpoints rather than aging broadlyMaking longevity medicine accessible through disease-focused approaches and data-driven validationPersonal motivation: Sergey's experience as a rare disease patient and the urgency of advancing treatmentsQuotes:"Longevity as an industry is by far the industry with the biggest added value out there, because that is the issue that we all share. Without solving these things, none of the other stuff really matters—not FinTech, not blockchain, not sustainability.""Five scientists in a room generally don't make a company. Prolonging rodent lives does not make a company either.""The ultimate longevity drug version 1.0 would be a therapeutic which has an original disease indication, which also has somehow cracked the mechanism of action that would be translatable across several age-related disease domains.""It is extremely arrogant for the space to say that we're not interested in age-related diseases, like we're not interested in curing the diseases. That's traditional biotech. We're not that. We are the longevity space.""Pharma is still thinking in terms of assets rather than processes. It is almost impossible to sell a process to them... What pharma still wants is the result of that capacity actually coming to life.""At the point when something has happened to you and a rare disease has happened to you... you're only equipped with that standard of treatment that is currently available and that has made it to the clinic.""I think the presence of the FDA as this kind of gatekeeper-type agency saying, 'No, you cannot go after aging in a romanticized way. You actually need to focus yourself'—that benefits the field much more than it hurts the field."
- Jul 9, 202547 min
Molecules to medicine: The translational landscape of aging interventions (Panel discussion at BAAM 2025)
In this special episode, host Chris Patil (VP-Media, BioAge) moderates a live panel discussion at the 25th Bay Area Aging Meeting at UCSF, bringing together six leading voices across the aging research ecosystem to tackle one of the field's most critical challenges: how to move promising discoveries from the laboratory to therapies that can benefit patients.The distinguished panel spans academia, industry, and scientific publishing, featuring Janine Sengstack (CEO, Junevity), Saul Villeda (Professor, UCSF), Jodi Nunnari (Director, Bay Area Institute of Science, Altos Labs), Sebastien Thuault (Chief Editor, Nature Aging), Anne Brunet (Professor, Stanford), and Nir Barzilai (Professor, Albert Einstein College of Medicine). Together, they explore the most promising research directions for clinical impact, the revolutionary tools enabling modern aging research, and the structural challenges that must be overcome to bring longevity therapies to market.Listeners will gain insights into the emerging science of cellular rejuvenation, the importance of systemic factors in aging, how to balance high-risk discovery with practical drug development, and the cultural shifts needed to better prepare the next generation of scientists for translational work. The panel also addresses the regulatory challenges of targeting aging itself as an indication and offers candid advice for young researchers navigating this rapidly evolving field.The Finer Details:Emerging research directions with the greatest clinical potential: cellular senescence, rejuvenation and repair, DNA methylation clocks, and understanding what makes aging biomarkers tickThe revolution in cellular and spatial resolution tools and how single-cell technologies are revealing cell-type-specific aging responsesSystemic factors and the remarkable plasticity remaining in aging organisms that can be unlocked through interventionsThe critical importance of starting with human data and working backward to validate targets and approachesChallenges unique to aging biotech: the need for aging-specific cellular assays, testing in older animal models, and genetic validationCultural and structural barriers between academia and industry, including the shift from mechanism-focused to mission-driven researchBalancing high-risk fundamental discovery with the practical needs of drug development and clinical translationThe regulatory landscape for aging interventions and potential pathways to FDA approval beyond traditional disease indicationsAdvice for young scientists: embracing rejection as part of the process, finding passion, working as teams, and considering diverse career paths in the growing longevity ecosystemQuotes:"Our goal as a company is to increase human health span, and the way I like to frame that more colloquially is we want to increase the number of happy, healthy years each person gets to spend on Earth." - Janine Sengstack"There is an exquisite amount of plasticity left in an aging organism, both within the tissues, within the cells. There is plasticity that we can actually tap into." - Saul Villeda"Burn bright, but don't burn out." - Jodi Nunnari"The challenge that we run into is that there are so many combinations that very quickly it would become intractable to line up enough test tubes to test them all." - Sebastien Thuault, on the complexity of aging interventions"We love our job. If not, we would not be doing it. I would do it again in a heartbeat... you get paid to play, to ask the questions that interest you, the approaches that interest you to play with who you want to—it is a fantastic job." - Saul Villeda"Our life is a life of rejection...and still, we're having fun and making an advance. So don't give up." - Nir Barzilai
- Jun 4, 202537 min
Partial epigenetic reprogramming: the "holy grail" for aging therapeutics (Michael Ringel, Life Biosciences)
Michael Ringel is the Chief Operating Officer of Life Biosciences, a biotechnology company pioneering cellular rejuvenation therapies to reverse and prevent multiple diseases of aging. Michael became COO of Life just a few months ago, but he's been advising the company since 2018. Prior to this year, he was managing director and senior partner at Boston Consulting Group (BCG), where over a 25-year career he focused on R&D and innovation initiatives across the private sector and government. He earned his PhD in biology at Imperial College London and a JD from Harvard Law, and has become an active and highly respected member of the global longevity biotech community.In this episode, Chris and Michael explore Life Biosciences' groundbreaking approach to partial epigenetic reprogramming - the "holy grail" technology that could transform how we age at cellular, tissue, and organism levels. They discuss how this approach taps into the same biology that makes babies young, Life's lead therapeutic candidate ER-100 for eye diseases, and the "pipeline in a pill" concept at the core of the geroscience hypothesis: the idea that enable single interventions based on longevity science could treat multiple age-related diseases simultaneously.The Finer Details:The biology behind partial epigenetic reprogramming and how it differs from full reprogramming to pluripotencyWhy Michael considers partial reprogramming the "holy grail" of longevity interventionsLife Biosciences' lead candidate ER-100 for glaucoma and NAION (non-arteritic anterior ischemic optic neuropathy)The innovative inducible system that allows the therapy to be turned on and off with doxycyclineWhy the eye represents an ideal starting point for reprogramming therapiesThe "pipeline in a pill" concept and geroscience hypothesis - how single interventions could treat multiple age-related diseasesParallels between the emerging longevity field and the massive GLP-1 drug market that many pharma companies missedThe role of philanthropic investment in advancing fundamental longevity researchEvolutionary theories of aging and why aging should be easily manipulableTimeline expectations for moving from single disease treatments to whole-body rejuvenationLinksLife Biosciences company websiteMichael Ringel's ARDD talk
- Apr 2, 202536 min
Cell Reset Therapeutics to Extend Healthspan and Lifespan (Janine Sengstack, Junevity)
Dr. Janine Sengstack is the Chief Scientific Officer and co-founder of Junevity, a company created in 2023 with the mission of extending health span and lifespan through what they term "Cell Reset therapeutics." The company recently secured $10 million in seed funding.In this episode, Chris and Janine explore the innovative platform Janine developed during her PhD work in Hao Li's lab at UCSF, which now forms the foundation of Junevity's therapeutic approach. They discuss how the company uses computational and experimental methods to identify transcription factors that can "reset" cells from a diseased, aged state back to a healthy state while maintaining cell identity. Janine explains how Junevity is developing siRNA therapeutics targeting these transcription factors to treat age-related diseases, with a focus on metabolic conditions and other disorders that impact longevity.The Finer Details:The development of the Reset platform during Janine's PhD work and its evolution into Junevity's therapeutic approachHow transcription factors act as "managers" in cells, regulating many other genesUsing AI and machine learning to identify the right transcription factors to target based on disease and tissue-specific dataThe validation process for siRNA therapeutic candidates in cell and animal modelsJunevity's focus on diseases with large-scale transcriptional dysregulation, including type 2 diabetes, obesity, muscle wasting diseases, and osteoarthritisThe advantages of siRNA as a therapeutic modality for targeting traditionally "undruggable" transcription factorsJunevity's business strategy and timeline, with clinical trials potentially beginning in 2026Quotes:"We tackled this high risk, high reward PhD project: we were inspired by the Yamanaka factors to say, 'Okay, let's find brand new transcription factors that we can target to take cells from a diseased, old state and bring them back to a healthy state while keeping them the same cell type, never turning them into a stem cell.'""Transcription factors: I like to think of them as managers in the cell.""We think the advent of modern AI and machine learning tools to better analyze what they regulate, plus siRNA as a really well-proven therapeutic modality, really unlocks the ability to target transcription factors and really make powerful therapeutics with them.""We're thinking about using transcriptional regulation as a way to come up with novel therapeutics to treat diseases that have a big impact on people's health span and lifespan.""We want to advance our programs towards development candidates, which basically means the drug entity, and move them forward towards clinical development as fast as possible.""I would love if we had multiple siRNA drugs on the market, ideally, or in late stages of development for a wide range of longevity-related diseases... We think that there's really huge potential here for making a big impact on a lot of different really complicated diseases."Linkshttps://www.junevity.com
- Jan 9, 202540 min
Building the Infrastructure for Longevity Medicine: ARPA-H's PROSPR Program (Dr. Andrew Brack, Program Manager)
Dr. Andrew Brack, Program Manager at the Advanced Research Projects Agency for Health (ARPA-H), discusses PROSPR (Proactive Solutions for Prolonging Resilience), an ambitious new program aimed at extending human healthspan. In this wide-ranging conversation, Chris and Andrew explore how PROSPR plans to accelerate the development of therapies that target aging itself by building the regulatory and scientific infrastructure needed to measure and improve health during aging. They discuss PROSPR's innovative approaches to in-home data collection, biomarker development, and clinical trial design that could compress decades-long studies into just three years.The Finer Details:The mission and structure of ARPA-H as a catalyst for healthcare innovationHow PROSPR aims to build "train tracks" for the longevity therapeutics industryThe program's novel approach to measuring health through intrinsic capacityStrategies for compressing clinical trials from decades to yearsThe economic impact of extending healthspan by just one yearPlans for first- and second-generation therapeutics targeting agingThe role of in-home health monitoring in future clinical trialsQuote: "We have this moral imperative to close the gap between the length that we are living and the number of years that we're living in good health."Links:PROSPR websiteProposers' Day registration
- Nov 20, 202426 min
Decoding Stem Cell Rejuvenation Factors (Markus Gstöttner, CEO of Clock.bio)
Markus Gstöttner is the CEO of Clock.bio, a company devoted to extending and improving the quality of life by reversing the harmful effects of time in our cells. In this episode, Gstöttner shares how his company is working to extend healthspan by understanding and harnessing the natural rejuvenation capabilities of stem cells. The conversation explores Clock.bio's groundbreaking approach to identifying the genes and pathways involved in cellular rejuvenation, and their vision for translating these discoveries into therapies.The Finer Details:How induced pluripotent stem cells (iPSCs) naturally resist and reverse agingClock.bio's novel platform for forcing stem cells to age and studying their spontaneous rejuvenationThe company's comprehensive genetic screen identifying over 150 rejuvenation-related genes, the Atlas of Rejuvenation FactorsStrategies for validating these discoveries and developing therapeutic applicationsThe path from discovery to clinical trials for extending human healthspan
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About Translating Aging
On Translating Aging, we talk with the worldwide community of researchers, entrepreneurs, and investors who are moving longevity science from the lab to the clinic. We bring you a commanding view of the entire field, in the words of the people and companies who are moving it forward today. The podcast is sponsored by BioAge labs, a clinical-stage biotechnology company developing therapies to extend human healthspan by targeting the molecular causes of aging.
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