PhD at MIT: The Longevity Molecule That Reverses Aging (250 Studies)
Dave Asprey
Aug 19, 2025
Episode description
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 T
Mindsip insights from this episode:
Utilize advanced biological age clocks for accurate health predictions
The most advanced biological age clocks now incorporate blood analytes like glucose and cholesterol along with DNA methylation data for a more accurate prediction.
Avoid calorie restriction to maintain muscle mass and immunity
While calorie restriction can extend lifespan in lab animals, in humans it can lead to low muscle mass and a weakened immune system, increasing vulnerability to infectious diseases.
Activate mitochondrial health with Signal supplement
The supplement 'Signal' combines NMN with Honokiol, a compound that specifically activates the mitochondrial sirtuin SERT3 to help fight oxidative damage.
Consider NAD booster to alleviate menopause symptoms
An unpublished pilot study suggests that the NAD-boosting supplement Basis may reduce symptoms of menopause, such as hot flashes.
Recognize mitochondria's role in aging through sirtuins
The fact that three out of seven human sirtuin proteins are located in the mitochondria is strong evidence for the mitochondria's central role in aging.
Address high homocysteine to prevent brain shrinkage
High homocysteine is not just a signal of a problem but is an active culprit that can cause brain shrinkage, which can be mitigated with a specific B-vitamin complex.
Utilize poised populations to accelerate longevity trials
Longevity trials can use 'poised populations,' like obese people, to see the effects of an intervention faster because they experience aging-related issues at a younger age.
Choose pterostilbene for superior bioavailability over resveratrol
Pterostilbene is more bioavailable and effective at lower doses than resveratrol because its chemical structure allows it to get into cells more easily.
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