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: podcast@biohagelabs.com

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+