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Unveiling the Secrets of Small Molecules for Longevity

Watch or listen to the full podcast episode on Spotify:

Welcome to the Human Longevity Podcast, hosted by Dr. Melissa Petersen. In this episode, we embark on a fascinating journey into the world of small molecules and their impact on the aging process. We will dive into groundbreaking research and data to separate the hype from reality when it comes to slowing down biological aging. (1)

Our special guest for today is Tom Weldon, the founder and CEO of Ponce de Leon Health and the CEO of Rejuvant. Tom’s unique perspective and insights are going to shed light on a topic that affects us all – our own longevity.

The Quest for a Game-Changer

Tom’s journey into the world of longevity began with a search for a project worth investing in. He scoured various research areas, looking for something that could truly make a difference. Initially, the field seemed too risky, long-term, and costly for traditional venture capital. However, two crucial events changed his perspective.

First, a physician approached him with the idea of researching vitamin D3, which had shown a remarkable 30% increase in lifespan in a model organism. Tom saw the potential for something practical and accessible to everyone – a key factor in making real progress against aging. (3)

Then, a lecture on Alzheimer’s disease led to a revelation. Aging, like Alzheimer’s, is incredibly complex and multifactorial. If a single drug were the solution, it would have been discovered already. Tom began to consider the possibility that a compound, not classified as a drug, could influence aging.

The Birth of Ponce de Leon Health

With this newfound perspective, Tom founded Ponce de Leon Health, aiming to explore the potential of natural supplements, vitamins, and minerals in the realm of longevity. He initiated a comprehensive research project to identify compounds that had been shown to extend lifespan in various organisms, from yeast to primates.

The Unveiling of Small Molecule Secrets

The research yielded a list of 33 compounds that had demonstrated increased lifespan in scientific studies. These compounds were subjected to rigorous testing in the Caenorhabditis elegans model, revealing some remarkable findings.

Interestingly, more was not always better. Beyond a certain point, adding more compounds became toxic and counterproductive. Few compounds demonstrated additive effects, and some even canceled each other out. This research highlighted the complexity of aging and the need for a more nuanced approach.

Alpha-Ketoglutarate: The Critical Player

Among the tested compounds, calcium alpha-ketoglutarate emerged as a powerhouse. It exhibited a significant impact on longevity, and when combined with methylated B, and Vitamin A in women and with vitamin D3 in men, it formed the basis of what would become the most powerful age reversal supplement on the market that actually works and has been proven in human studies at the Bucks Institute of Aging. This product is now known as Rejuvant. (4)

The Epigenetic Connection

Further research delved into epigenetics – the changes in methylation patterns in DNA that occur with aging. These patterns strongly correlate with chronological age. The groundbreaking discovery was that calcium alpha-ketoglutarate played a vital role in reversing these patterns. (1)

Rejuvant: A Transformational Solution

Rejuvant, powered by calcium alpha-ketoglutarate, has demonstrated impressive results. It has been shown to increase health span by 41%, extend lifespan by 12-15%, and, most strikingly, achieve an average of an eight-year biological age reversal in just eight months of use. (4)

A Paradigm Shift

In a recent article published in Aging (1), alpha-ketoglutarate, the foundational patented ingredient in Rejuvant’s efficacy was confirmed, solidifying its status as a true game-changer in the field of longevity. Notably, it outperformed other well-known molecules like resveratrol, rapamycin, and NAD+ precursors like NMN.

The Key Takeaway: A New Era in Longevity

Tom’s journey and the research behind Rejuvant underscore a fundamental shift in our understanding of aging. It’s not about adding more repair mechanisms; it’s about providing the essential substrate for those mechanisms to function optimally.

Rejuvant, with its focus on epigenetic reversal, is at the forefront of this revolution. It’s not about taking a stack of supplements but ensuring that the critical transportation system within our bodies is functioning at its best.

As we wrap up this episode, we leave you with this essential message: Less can indeed be more when it comes to supplements. Understand why you’re taking what you’re taking, and make sure it aligns with your health goals. The future of longevity may be simpler and more accessible than we ever imagined.

Thank you for joining us on this enlightening journey into the small molecules of longevity. We’ll be back soon with more insights and discoveries to help you live better, longer. Stay tuned!


  1. Yang, J. H., Petty, C. A., Dixon-McDougall, T., Lopez, M. V., Tyshkovskiy, A., Maybury-Lewis, S., … & Sinclair, D. A. (2023). Chemically induced reprogramming to reverse cellular aging. Aging, 15.
  2.  Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. cell, 131(5), 861-872.
  3. Huggins B, Farris M. Vitamin D3 promotes longevity in Caenorhabditis elegans. Geroscience. 2023 Feb;45(1):345-358. doi: 10.1007/s11357-022-00637-w. Epub 2022 Aug 24. PMID: 36001277; PMCID: PMC9886739.
  4. Demidenko O, Barardo D, Budovskii V, Finnemore R, Palmer FR, Kennedy BK, Budovskaya YV. Rejuvant®, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test. Aging (Albany NY). 2021 Nov 30;13(22):24485-24499. doi: 10.18632/aging.203736. Epub 2021 Nov 30. PMID: 34847066; PMCID: PMC8660611.


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