Learn how to slow, and even reverse, your biological age with cutting-edge science on the molecule that controls your longevity. Host Dave Asprey sits down with Dr. Leonard Guarente, an MIT PhD and one of the most respected longevity researchers in the world, to reveal how NAD+, sirtuins, and DNA methylation clocks can help you hack aging, upgrade your mitochondria, and extend your healthspan. This episode gives you the real science, proven by over 250 studies, behind supplements, nutrition, and biohacking tools that actually work for brain optimization, metabolism, and human performance.
Watch this episode on YouTube for the full video experience:
https://www.youtube.com/@DaveAspreyBPR
You’ll learn why NAD+ is a master regulator of mitochondrial health, how DNA methylation clocks accurately measure biological age, and why boosting sirtuin activity improves resilience, neuroplasticity, and recovery. Dr. Guarente shares insider strategies from decades of functional medicine research, including nootropics, targeted supplements, fasting protocols, and diet adjustments from carnivore to Mediterranean that can shift your metabolism toward longevity. Dave and Dr. Guarente explore advanced biohacks like cold therapy, sleep optimization, and ketosis, plus how to balance these interventions with your genetics, lifestyle, and health goals. You’ll also hear about the surprising role of homocysteine in brain aging, how to use lab testing to guide your longevity plan, and why resilience is the ultimate measure of health.
You’ll learn:
• How emotional repression affects brain function, metabolism, and decision-making
• Tools for nervous system regulation and emotional healing that drive high performance
• Why most people fail without emotional intelligence and internal safety
• How somatic awareness can optimize your energy, focus, and relationships
• The science of fear, trauma release, and how to turn discomfort into growth
• How to coach yourself out of stress, shame, and negative self-talk
Whether you want to sharpen your brain, protect your heart, or upgrade your energy systems, this is a masterclass in smarter not harder biohacking for a longer, higher-performing life.
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 is the top podcast for people who want to take control of their biology, extend their longevity, and optimize every system in the body and mind. Each episode features cutting-edge insights in health, performance, neuroscience, supplements, nutrition, hacking, emotional intelligence, and conscious living.
Episodes are released every Tuesday, Thursday, and Friday (audio-only) where Dave asks the questions no one else dares, and brings you real tools to become more resilient, aware, and high performing.
Keywords: NAD+ supplementation, Sirtuin activation, DNA methylation clocks, Biological age testing, Mitochondrial biogenesis, Epigenetic reprogramming, Pterostilbene benefits, Nicotinamide riboside (NR), Nicotinamide mononucleotide (NMN), Homocysteine reduction, Oxidative stress repair, Superoxide dismutase (SOD) activation, Functional medicine longevity, Healthspan optimization, Resveratrol bioavailability, Menopause mitochondrial support, Phenylbutyrate and protein folding, High-fat diet longevity studies, Neurodegenerative disease biohacking, INCHIANTI aging study
Thank you to our sponsors!
Resources:
• Elysium Website. Use code ‘UPGRADE25’ for 25% off the first month of a monthly subscription to any Elysium supplement: https://www.elysiumhealth.com/
• Dave Asprey’s Website: https://daveasprey.com
• Danger Coffee: https://dangercoffee.com/DAVE15
• Dave Asprey’s BEYOND Conference: https://beyondconference.com
• Dave Asprey’s New Book – Heavily Meditated: https://daveasprey.com/heavily-meditated
• Upgrade Collective: https://www.ourupgradecollective.com
• Upgrade Labs: https://upgradelabs.com
• 40 Years of Zen: https://40yearsofzen.com
Timestamps:
0:00 — Introduction to NAD & Sirtuins
0:59 — Intro
7:04 — Animal vs Human Aging Studies
10:07 — Discovery of Sirtuins
14:43 — NAD’s Role in Aging
15:34 — Resveratrol vs Pterostilbene
23:13 — Timing NAD Supplementation
36:34 — Diet & Lifestyle Factors
50:05 — Elysium’s Basis & Signal
1:00:03 — Future Clinical Trials
1:05:14 — Psychology of Aging & Wrap-Up
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The Human Upgrade: Biohacking for Longevity & Performance 
