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.
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
Resources:
• Elysium Website. Use code ‘UPGRADE25’ for 25% off the first month of a monthly
subscription to any Elysium supplement: https://www.elysiumhealth.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
Connect with Dave Asprey!
Website: https://daveasprey.com
TikTok: https://www.tiktok.com/@daveaspreyofficial
Instagram: https://www.instagram.com/dave.asprey/
Facebook: https://www.facebook.com/Daveaspreyofficial/
X: https://x.com/daveasprey
YouTube: https://www.youtube.com/c/daveaspreybpr
The Human Upgrade Podcast: https://www.instagram.com/TheHumanUpgradePodcast/ https://m.facebook.com/Thehumanupgrade/
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/
Dave’s favorite supplements: https://www.shopsuppgradelabs.com/discount/DAVE15
Upgrade Collective: https://www.ourupgradecollective.com
Upgrade Labs: https://upgradelabs.com
40 Years of Zen: https://40yearsofzen.com
