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 others
• The "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 regenerative
• Why 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 indications
• Phase 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 skin
• The richness of the translational dataset: biopsies, tape-stripping, spatial transcriptomics, proteomics, multiplex histomics, plasma biomarkers — all feeding back into ALEMBIC to refine the platform
• Why 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 reversal
• The Rubedo–Beiersdorf partnership and the cosmetic vertical as a parallel commercial axis
• Pipeline beyond skin: targeting aberrant basaloid stem cells in IPF and other pulmonary indications using different modalities (prodrugs, PROTACs, ADCs) to achieve cell-state selectivity
• The 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 modulation

Quotes:

"There is not such a thing as a senescent cell — like there is not a cancer cell. And that was the initial idea. I'm glad that over time the field evolved. Now this is an accepted concept in the senotherapeutic space."

"We are really talking about a dual function of RLS-1496 that can modulate the cell state depending on the adaptive response. That's why we call this — de facto — a new class of senotherapeutics. We call them adaptive senotherapeutics, or senoadaptive drugs — not a senolytic or a senomorphic, but working by modulating the cell state."

"The best animal model for human therapies is human. As much as you can do preclinical work in animal models, it's always an approximation. We were able to test this directly in patients for safety, and in 4 out of 4 indications, we didn't have any safety signal."

"Imagine you're taking care of a growing tree, and this tree has some dead leaves and some are a little bit stressed. If you shake the tree, the dead leaves will fall; the healthy leaves will not, because they're healthy and they resist the shake. But that shake actually gives the stressed leaves space and breathing room, and helps them to regain vitality. That's a little bit what GPX4 modulation does."

"Senotherapeutics is a large, growing field — an untapped therapeutic opportunity. There is no such thing as a pan-senolytic or a pan-senotherapeutic, like there is no pan-oncotherapeutic. You need to understand the context. But these will all be part of the arsenal for true longevity medicine."

"I don't see this as prevention of disease. The way I see therapies like ours, and the way the field of longevity is developing, is treating diseases decades before they develop. That's not a new concept — that's what we're doing in diabetes. You can be diagnosed with prediabetes today and reverse those biomarkers with lifestyle changes or metformin, and maybe never develop diabetes. That's exactly what we're doing here."

"First of all, celebrating the first approved drugs from Rubedo — I don't think we're too far from that. But that's also a beginning, because you learn from the big momentum the GLP-1 agonists created: how a drug can start in one indication, create a new field, and prove that you can go beyond that. I hope in a few years we come back and talk about the next GLP-1 — this could be GPX4 modulators, or the senoadaptive drugs that are first in our pipeline."

Links:

• Rubedo Life Sciences: https://www.rubedolife.com
• Marco Quarta's previous appearance on Translating Aging: Ep 35 — Targeting Pathologic Cells to Preserve Biological Youth

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 investor
• LongeVC's pragmatic philosophy: targeting specific diseases rather than aging as a whole
• The convergence of biotech, regenerative medicine, and AI in the longevity space
• Key criteria for early-stage investment: disease indication, balanced teams, clean IP transfer
• Why "five scientists in a room" and "great mouse data" don't make an investable company
• The importance of platforms having their own pipelines, not just service models
• How LongeVC's scientific advisory board (including Alex Zhavoronkov, Vadim Gladyshev, Thomas Rando) evaluates investments
• Success stories: Rubedo's senolytic partnership and Turn Bio's epigenetic reprogramming deal
• The 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 broadly
• Making longevity medicine accessible through disease-focused approaches and data-driven validation
• Personal motivation: Sergey's experience as a rare disease patient and the urgency of advancing treatments

Quotes:

"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."

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 tick
• The revolution in cellular and spatial resolution tools and how single-cell technologies are revealing cell-type-specific aging responses
• Systemic factors and the remarkable plasticity remaining in aging organisms that can be unlocked through interventions
• The critical importance of starting with human data and working backward to validate targets and approaches
• Challenges unique to aging biotech: the need for aging-specific cellular assays, testing in older animal models, and genetic validation
• Cultural and structural barriers between academia and industry, including the shift from mechanism-focused to mission-driven research
• Balancing high-risk fundamental discovery with the practical needs of drug development and clinical translation
• The regulatory landscape for aging interventions and potential pathways to FDA approval beyond traditional disease indications
• Advice for young scientists: embracing rejection as part of the process, finding passion, working as teams, and considering diverse career paths in the growing longevity ecosystem

Quotes:

"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

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 pluripotency
• Why Michael considers partial reprogramming the "holy grail" of longevity interventions
• Life 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 doxycycline
• Why the eye represents an ideal starting point for reprogramming therapies
• The "pipeline in a pill" concept and geroscience hypothesis - how single interventions could treat multiple age-related diseases
• Parallels between the emerging longevity field and the massive GLP-1 drug market that many pharma companies missed
• The role of philanthropic investment in advancing fundamental longevity research
• Evolutionary theories of aging and why aging should be easily manipulable
• Timeline expectations for moving from single disease treatments to whole-body rejuvenation

Links

• Life Biosciences company website
• Michael Ringel's ARDD talk

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 approach
• How transcription factors act as "managers" in cells, regulating many other genes
• Using AI and machine learning to identify the right transcription factors to target based on disease and tissue-specific data
• The validation process for siRNA therapeutic candidates in cell and animal models
• Junevity's focus on diseases with large-scale transcriptional dysregulation, including type 2 diabetes, obesity, muscle wasting diseases, and osteoarthritis
• The advantages of siRNA as a therapeutic modality for targeting traditionally "undruggable" transcription factors
• Junevity's business strategy and timeline, with clinical trials potentially beginning in 2026

Quotes:

"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."

Links

https://www.junevity.com

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 innovation
• How PROSPR aims to build "train tracks" for the longevity therapeutics industry
• The program's novel approach to measuring health through intrinsic capacity
• Strategies for compressing clinical trials from decades to years
• The economic impact of extending healthspan by just one year
• Plans for first- and second-generation therapeutics targeting aging
• The role of in-home health monitoring in future clinical trials

Quote: 

"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 website

Proposers' Day registration

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 aging
• Clock.bio's novel platform for forcing stem cells to age and studying their spontaneous rejuvenation
• The company's comprehensive genetic screen identifying over 150 rejuvenation-related genes, the Atlas of Rejuvenation Factors
• Strategies for validating these discoveries and developing therapeutic applications
• The path from discovery to clinical trials for extending human healthspan

Adam Freund (CEO) and Remi Laberge (CTO) are the founders of Arda Therapeutics, a biotechnology company developing novel therapies that selectively eliminate harmful cell populations driving chronic diseases. In this episode, they discuss their innovative approach to treating conditions like idiopathic pulmonary fibrosis by identifying and removing specific cell types that cause tissue damage, rather than trying to modify cellular behavior through traditional drug approaches.

The Finer Details:

• The concept of pathogenic cells as drivers of chronic disease
• How single-cell RNA sequencing enables precise identification of harmful cell populations
• Arda's approach to developing targeted antibody therapeutics
• Advantages of cell elimination versus pathway modification
• The potential for intermittent dosing to improve patient quality of life
• Future applications in aging and age-related diseases

Quotes: 

"Cells make up tissues. Tissues make up organisms... If you have the right cell at the right place, everything looks good. If you have the wrong cell at the wrong place, doing the wrong thing, the tissue will decay."

"We position our strategy as an alternative to traditional pathway targeting... changing cell behavior by blocking a single node could be quite challenging."

"This is game changer for the patient experience. If we're successful, our drug will be administered once a quarter, once every six months. But during that time, this patient feels like he is not a patient. He doesn't take a drug, he's not under treatment, and doesn't have the side effect of taking those drugs."

"We think that cell depletion is a broadly applicable strategy across many chronic diseases, including potentially aging itself one day."

"In 10 years from now... we will know precisely which cells to eliminate. Now, will we be allowed to do it in an otherwise healthy patient? That's a different type of question."

Alex Aravanis is the CEO and co-founder of Moonwalk Biosciences, a biotechnology company pioneering precision epigenetic medicines. In this episode, Chris and Alex discuss Moonwalk's innovative approach to developing a new class of medicines aimed at treating complex diseases and potentially extending human healthspan.

The Finer Details:

• The concept of epigenetics as the "source code" for cell states
• Moonwalk's technology for analyzing and modifying the epigenome
• The company's focus on cardiometabolic diseases and adiposity
• Comparison of Moonwalk's approach to other epigenetic reprogramming strategies
• Potential applications in treating obesity and metabolic disorders
• The use of AI and machine learning in epigenetic research
• Future directions and challenges for Moonwalk Biosciences

Quotes:

Quotes have been lightly edited for clarity.

"In the past, I've heard people refer to the DNA as the blueprint of biology, and I don't quite like that analogy. I think of it as more like the hardware, and the epigenome is the source code — the epigenome is responsible for the complex coordination of different genes that lead to proteins, and the temporal aspects of those so it's really how the hardware is used to make and maintain and change different cell types."

"We're opening up the epigenome as a platform for drug discovery. The vast majority of the genome is not the coding regions, but it's incredibly important in controlling gene expression. So there's a lot of biology in there to inform our selection of targets, and we think that could dramatically improve both the number of interesting targets and our ability to select targets. The data that we're creating, our expertise, and our computational tools make us amongst the best in the world at using the epigenome for drug discovery."

Links:

Email questions, comments, and feedback to: [email protected]

Translating Aging on Twitter: @bioagepodcast

BioAge website: https://bioagelabs.com

BioAge Twitter: [@bioagelabs]

In this episode, Chris Patil speaks with Dr. Mehmood Khan, CEO of Hevolution Foundation, about the organization's mission to extend healthy human lifespan and better understand the aging process. Dr. Khan discusses Hevolution's unique approach to funding global scientific discovery and investing in private companies dedicated to advancing aging science. He shares insights into the challenges and opportunities in the field of longevity research, the importance of global collaboration, and the potential impact of extending healthspan on societies worldwide.

The Finer Details:

• Hevolution Foundation's origin and mission
• The importance of aging research in the context of global challenges
• Hevolution's collaborative approach and funding strategies
• Challenges in translating aging research into accessible interventions
• The need for validated biomarkers in aging research
• Global perspectives on aging, including challenges in developing countries
• The importance of policy engagement and public awareness in advancing the field

https://www.hevolution.com/

Hans Keirstead, PhD, is the Chairman of the Board at Immunis, a biotechnology company researching and developing immune secretome products to address age-driven immune deficits. In this episode, Chris and Hans discuss Immunis' approach to targeting the aging immune system as a key driver of age-related disease. They explore the potential of immune secretome factors to restore youthful immune function, the promising results from Immunis' preclinical and early clinical studies, and the future of immune-modulating therapeutics to extend healthspan.

THE FINER DETAILS

• The critical role of the immune system in the aging process and age-related disease
• Immunis' focus on immune precursor cell secretome factors to restore youthful immune function
• Preclinical studies demonstrating the effects of Immunis' secretome product on muscle growth, metabolism, and inflammation in aged mice
• Early results from Immunis' Phase 1/2a clinical trial in older adults with muscle atrophy and knee osteoarthritis
• The potential for immune secretome therapeutics to treat a wide range of age-related conditions and enhance healthspan
• The importance of developing affordable and accessible therapies to maximize impact

QUOTES

• "Every manifestation of aging is immunologically mediated. It's phenomenal. When one ages, your immune system in 100% of humans gets angry, so becomes highly pro-inflammatory."
• "Our drug is not a stem cell. It's not an immune cell. It is the secretion set, that same secretion set that you and I have, and everyone on this earth has, that precipitously declines with age, and now we're able to restore it."
• "We showed that IMMUNA fundamentally changes gene expression in order to promote the expression of genes for growth and regeneration. And then it inhibits the expression of genes that inhibit growth and regeneration."
• "I believe that this [secretome therapeutic] is going to be taken prophylactically by most humans, every quarter or so, to keep their immune system young, keep their immune system in a prophylactically competent state."
• "I want this thing to be available to everyone who wants it at an extremely low price, so that we can keep people alive, so that we can keep them disease free, so they can have productive years in their golden times, in their older age."

LINK TO PAPER

Stem cell secretome treatment improves whole-body metabolism, reduces adiposity, and promotes skeletal muscle function in aged mice