Translating Aging

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

Dr. Daisy Robinton, co-founder and CEO of Oviva Therapeutics, discusses the company's innovative approach to improving women's healthspan by targeting the biology of ovarian aging. Motivated by her personal experiences and the realization that female physiology is underserved by research and medicine, Daisy outlines how menopause is a key inflection point in the acceleration of aging in women. She explains the central role of anti-Mullerian hormone (AMH) in regulating ovarian function and fertility. Oviva's lead program, a recombinant enhanced AMH protein, aims to improve IVF outcomes by synchronizing follicle growth. Excitingly, this approach could also preserve ovarian reserve to delay menopause onset, thereby extending female healthspan.

Key Topics Covered:

• Pivoting from developmental biology to found a women's health startup
• Ovaries as central regulators of female healthspan beyond reproduction
• AMH as a brake on follicle activation and loss of ovarian reserve
• Using enhanced AMH to improve egg yield in poor-responding IVF patients
• Potential of AMH-based therapy to delay menopause and slow aging
• Menopause as the single greatest known accelerator of aging
• Economic and societal impact of extending female healthspan
• Distinguishing reproductive longevity from overall women's health
• Viewing fertility as a marker of overall health and wellbeing

Dr. Noah Davidsohn, co-founder and CSO of Rejuvenate Bio, discusses the company's innovative work using gene therapies to treat age-related diseases in dogs and humans. In his conversation with host Chris Patil, he explains his recent groundbreaking study showing that partial cellular reprogramming with Yamanaka factors extended lifespan and healthspan in very old mice. Noah then outlines Rejuvenate's clinical pipeline, including targeting longevity pathways like FGF-21 for heart disease and combining TGF-beta inhibition with klotho for osteoarthritis. By choosing secreted factors deliverable with liver-targeted gene therapy, Rejuvenate hopes to circumvent delivery challenges. Noah conveys an inspiring vision of adding healthy years to dogs' and humans' lives.

Key Topics Covered:

• Rejuvenate Bio's mission to reverse aging and age-related disease
• Lifespan doubling in old mice with cyclic Yamanaka factor induction
• Controllable gene therapy system for in vivo partial reprogramming
• Choice of FGF-21 for pleiotropic effects deliverable from liver
• Lead programs for arrhythmogenic cardiomyopathy and mitral valve disease
• Advantages of treating age-related diseases first in dogs
• Combination gene therapy for osteoarthritis: TGF-beta and klotho
• Secreted proteins enable broad effects without broad delivery
• Vision of expanding healthspan by "squaring the curve"
• Potential to keep people healthy, active and productive to 100+

Drugs that target aging directly will fundamentally transform healthcare, and today, multiple drugs that impact key aging pathways are in clinical trials for obesity, CVD, and other metabolic diseases. A deeper understanding of human aging has the potential to identify new drug targets for disorders that affect the lives of hundreds of millions of people. 

On January 10, during JPM Healthcare Week, BioAge CEO Kristen Fortney moderated a panel of experts from biotech, pharma, and academia to discuss the challenges and opportunities of this exciting area, with topics including:

• Identifying new targets for chronic metabolic diseases by analyzing human aging
• Synergies between blockbuster GLP-1 drugs and compounds discovered through geroscience
• Ongoing and upcoming clinical trials of aging-targeted drugs for cardiometabolic indications

Moderator: 

• Kristen Fortney, PhD - CEO & co-founder, BioAge

Panelists:

• Michael Davidson, MD - CEO, NewAmsterdam Pharma
• Axel Haupt, MD - SVP Diabetes Clinical Development, Obesity, & Complications, Eli Lilly
• Tracey McLaughlin, MD - Professor, Stanford Medicine
• Rob Myers, MD - CMO, OrsoBio

30 Years of Aging Biology: A Pioneer’s Perspective (Cynthia Kenyon - VP Aging Biology, Calico Labs)

Dr. Cynthia Kenyon reflects on the evolution of the longevity field over the 30 years since the publication of her groundbreaking paper, “A C. elegans mutant that lives twice as long as wild type,” a genetic analysis of one of the first single-gene mutations to extend lifespan in the worm. She recounts the initial excitement and skepticism around the idea of a pathway that regulates aging, and subsequent validation of this and related ideas in a wide range of model organisms. She also discusses her longstanding belief in the translational potential to improve human healthspan, and her experience as a co-founder of one of the first longevity biotech startups, Elixir Pharmaceuticals, in 1999. Based on her unique historical perspective—and with undiminished enthusiasm—she looks ahead to the unsolved mysteries that will propel the next generation of breakthroughs.

Key ideas:

• Origins of looking at aging regulation in C. elegans in the 1990s
• age-1 and daf-2 as the first aging genes
• Early resistance to the idea of studying aging at the molecular level
• Cloning of genes to reveal conserved longevity pathways (IIS/mTOR)
• Extending lifespan in invertebrates, and then mice
• The connection between stress resistance to evolutionary theory
• Dr. Kenyon's initial belief in the translatability of aging science
• Co-founding Elixir Pharmaceuticals in 1999 to target aging
• Current optimism about interventions against aging
• Need for public funding of large trials of natural compounds
• Excitement about newest mechanisms like reprogramming
• The enduring promise of targeting core nutrient-sensing networks
• Developmental origins of aging rates and resilience

Links: 

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

Translating Aging on Twitter: @bioagepodcast

BioAge Labs Website bioagelabs.com

BioAge Labs Twitter @bioagelabs

BioAge Labs LinkedIn

Dr. Jamie Justice is Executive Director of the newly launched XPRIZE Healthspan, a $101 M international competition to accelerate therapeutics targeting aging biology. In conversation with host Chris Patil, Dr. Justice outlines the motivation, structure, and timeline of the prize, as well as how teams can get involved. She also explains unique aspects of this prize, including the public commentary period, how existing trials can be adapted for competition, functional endpoints, and judging criteria. She also conveys why coordination is needed to overcome barriers and drive investment in longevity R&D. Listeners will gain key insights into this ambitious initiative to catalyze progress translating research into treatments for aging.

Key ideas:

• Why aging solutions need acceleration despite increased attention
• The role and track record of incentive competitions like XPRIZE
• Motivation and sponsors enabling XPRIZE Healthspan ($101M purse)
• Timeline from conceptualization to upcoming 7-year active competition
• Expert endpoint committee setting measurable functional criteria
• Initial public commentary period for radical collaboration with teams
• Phases: Intent to compete, qualifying submissions, finalist selection
• Existing prevention trials can add program assessments
• Common data and protocols to validate findings across teams
• Goal of demonstrating restoration of function across domains
• Secondary judging criteria around accessibility, biomarkers
• Driving global coordination, investment, and innovation

Links: 

XPRIZE Healthspan

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

Translating Aging on Twitter: @bioagepodcast

BioAge Labs Website bioagelabs.com

BioAge Labs Twitter @bioagelabs

BioAge Labs LinkedIn