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+

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 podcast@bioagelabs.com

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 podcast@bioagelabs.com

Translating Aging on Twitter: @bioagepodcast

BioAge Labs Website bioagelabs.com

BioAge Labs Twitter @bioagelabs

BioAge Labs LinkedIn

Dr. Coleen Murphy is a prominent aging researcher and author of the upcoming book “How We Age: The Science of Longevity” from Princeton University Press. In this wide-ranging discussion, Coleen provides insights into her motivation for writing this book, key topics covered, and her unique perspective on the field.

Key ideas:

• Addressing ethical concerns about studying aging and longevity
• Defining aging conceptually and how metrics like lifespan vs. healthspan are measured
• Using genetics, transcriptomics and other tools to understand molecular changes in aging
• The prominent role of reproduction and sex differences in aging
• Theories on tradeoffs between reproduction and longevity
• Genetics of aging pathways including insulin/IGF-1, mTOR, and sirtuins
• Cellular processes involved in aging such as mitochondrial dysfunction, epigenetic changes, senescence
• The importance of models like C. elegans and Drosophila in aging research
• Ongoing research and future potential for interventions to increase healthspan
• The challenge of complex science without excessive jargon
• Highlighting critical contributions by women scientists in the field
• Omitting personal lifestyle advice and focusing on evidence-based science
• The rapid pace of advancement in biotech applications of longevity science

Links:

Email questions, comments, and feedback to podcast@bioagelabs.com

Translating Aging on Twitter: @bioagepodcast

BioAge Labs Website bioagelabs.com

BioAge Labs Twitter @bioagelabs

BioAge Labs LinkedIn

Dr. Nicholas Hertz is the co-founder and former CSO of Mitokinin, a biotech company developing therapies targeting damaged mitochondria in neurodegenerative disease. Mitokinin was recently acquired by pharmaceutical giant AbbVie. In this episode, Nick recounts the journey from academic research on PINK1 biology to founding a startup and advancing a clinical candidate. He provides insights into the drug discovery process, optimizing lead compounds, translating basic findings into therapies, and partnering with big pharma. Nick also shares lessons learned along the way about focusing on robust science, being adaptable, and maintaining ambition to help patients.

Key topics covered:

• Background on Mitokinin’s approach of activating PINK1 to clear damaged mitochondria
• Founding a company based on academic research and discoveries
• Navigating from tool compounds to optimizing in vivo activity and drug properties
• Using mitochondrial biomarkers like phospho-ubiquitin to track target engagement
• Partnering with AbbVie: alignment on science, IP transfer after acquisition
• Importance of reproducibility, following the science to clinic-ready agents
• Planning the next neurodegeneration startup based on past experience
• Advice for startups: pick projects wisely, focus on robust science over hype

Notable Quotes: (edited slightly for clarity and length)

"What PINK1 does is signal when mitochondria have gone bad and need to be cleared away."

"Seeing PINK1 mutations lead to early Parkinson's cemented the link between mitochondrial health and neurodegeneration."

"The biggest challenge was getting enough brain exposure and potency for in vivo efficacy."

"We developed assays to measure phospho-ubiquitin levels in patient samples and use it as a pharmacodynamic marker."

"With AbbVie, we were aligned on making a safe drug you'd feel comfortable giving to your own family."

"I enjoyed the journey more than the destination. Now I want to get back in the lab and do more science."

"Focus on projects you believe in and doing the most robust, reproducible science."

"I consider failing to help patients in Phase 3 trials a failure, even if you already exited successfully."

Links:

Mitokinin website (this link may become obsolete as Mitokinin becomes part of AbbVie)

Email questions, comments, and feedback to podcast@bioagelabs.com

Translating Aging on Twitter: @bioagepodcast

BioAge Labs Website bioagelabs.com

BioAge Labs Twitter @bioagelabs

BioAge Labs LinkedIn