Measuring programmatic aging with PRC2

Your biological age can drop by over three years in just eight weeks, and the tools to do it are already in your kitchen. This episode breaks down the cutting-edge science of methylation, polyphenols, Yamanaka mimetics, and epigenetic reprogramming that is rewriting what we know about anti-aging, longevity, and human performance. 

-Watch this episode on YouTube for the full video experience: https://www.youtube.com/@DaveAspreyBPR 

Host Dave Asprey sits down with Dr. Kara Fitzgerald, ND, IFMCP, a leading voice in functional medicine and epigenetic aging research. Her award-winning clinical studies published in Aging (2021, 2023, and 2025) proved that targeted diet and lifestyle interventions can measurably reverse biological age on validated epigenetic clocks. She is the author of Younger You, an IFM faculty member and Certified Practitioner, and one of the most rigorously credentialed researchers working at the intersection of functional medicine, nutrition, and longevity science today. 

Together, they go deep on Yamanaka factors, the Nobel Prize-winning discovery that can wind back a 90-year-old cell to its 20s, and the emerging class of compounds called Yamanaka mimetics, polyphenol-based supplements that may replicate some of those same cellular rejuvenation effects without the risks. They cover why polyphenols do the heavy lifting in biological age reversal, how AI is accelerating longevity research, and why the dark matter of nutrition may matter more than macros, carnivore protocols, or ketosis for long-term health. They also get into oxalates, mitochondria, fibroids, ovarian rejuvenation, and why the original Horvath clock may be more relevant than scientists thought. 

This is essential listening for anyone serious about biohacking, longevity, supplements, functional medicine, anti-aging, brain optimization, human performance, and using smarter not harder strategies to take control of your biology. 

You'll Learn: 

• How diet, supplements, and meditation reversed biological age by over three years in eight weeks in a randomized controlled trial 
• What Yamanaka factors are and why scientists are calling partial cellular reprogramming the future of anti-aging 
• Which polyphenols do the heaviest lifting for epigenetic rejuvenation, including EGCG, urolithin A, rosemary, marjoram, and yarrow 
• Why the Horvath epigenetic clock may actually be touching on programmatic aging rather than just exposomic wear and tear 
• How AI is unlocking patterns in longevity data that no human researcher could find alone 
• The problem with high-oxalate superfoods and how to get polyphenol benefits without the inflammatory downside 
• Why ovarian rejuvenation may be the highest-leverage Yamanaka application for women's longevity and brain health 
• How compounds like AKG, sodium butyrate, and forskolin may act as Yamanaka mimetics already available today 
• What the PRC2 polycomb clock reveals about programmatic aging and why it matters more than second-generation clocks 
• Why perimenopause does not have to be painful, and how functional medicine addresses it at the root 

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Dave Asprey is a four-time New York Times bestselling author, founder of Bulletproof Coffee, and the father of biohacking. With over 1,000 interviews and 1 million monthly listeners, The Human Upgrade brings you the knowledge to take control of your biology, extend your longevity, and optimize every system in your body and mind. Each episode delivers cutting-edge insights inhealth, performance, neuroscience, supplements, nutrition, biohacking, emotional intelligence, and conscious living. 

New episodes are released every Tuesday, Thursday, Friday, and Sunday (BONUS). Dave asks the questions no one else will and gives you real tools to become stronger, smarter, and more resilient. 

Keywords: Kara Fitzgerald, biological age reversal, epigenetics, DNA methylation, Yamanaka factors, polyphenols, EGCG, urolithin A, anti-aging, longevity, biohacking, functional medicine, supplements, mitochondria, epigenetic clock, cellular reprogramming, AKG, sodium butyrate, methylation, Steve Horvath, Vittoria Sebastiano, coleus, perimenopause, ovarian rejuvenation, pluripotent stem cells, PRC2, dark matter of nutrition, TRIM study, dihydroxyflavone, BDNF, Prenuvo, chemical cellular rejuvenation 

Resources:   

• Learn more about all of Dr. Fitzgerald’s work at: https://www.drkarafitzgerald.com/ 

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Timestamps:  

0:00 – Trailer 

1:28 – Explaining Study 

3:45 – What Is The Diet 

6:49 – Age Reversal 

8:17 – Polyphenols vs. Supplements 

9:27 – Food vs. Supplement Dosing 

12:41 – Oxalate & Polyphenol Trade-offs 

18:41 – Yamanaka Factors Explained 

28:59 – Chemical Cocktails 

32:15 – PRC2 Clocks & Programmatic Aging 

40:28 – Seasonal Eating 

43:40 – Carnivore Diet: Short vs. Long Term 

45:31 – Inuit Diet 

46:39 – Flavones & Brain-Crossing Compounds 

48:50 – Why Only Men in the Study? 

51:05 – Women, Perimenopause & the Protocol 

53:20 – Fibroids & Gaps in Women's Research 

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