David Sinclair's Longevity Protocol: A Guide to His Supplement Regimen

The Scientist Behind the Protocol

Professor David Sinclair, PhD, stands at the forefront of longevity research. As a tenured professor of genetics at Harvard Medical School and co-director of the Paul F. Glenn Center for Biology of Aging Research, Sinclair has pioneered a revolutionary approach to understanding the ageing process.

His extensive research on sirtuins (proteins that regulate cellular health and longevity) has garnered international recognition, including being named one of Time Magazine's 100 most influential people. Beyond his academic work, Sinclair has connected with millions through his bestselling book "Lifespan: Why We Age and Why We Don't Have To" and his transparent discussions about his personal supplement regimen.

"I don't want to just extend lifespan. I want to extend the healthy, vibrant years. Healthspan is just as important as lifespan." — David Sinclair, PhD

This comprehensive guide examines the key components of Sinclair's personal supplement protocol, the research supporting them, and practical ways to incorporate these elements into your own wellness routine.

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The Core Philosophy: The Information Theory of Ageing

Sinclair's approach to longevity centres around his "Information Theory of Ageing." This theory proposes that ageing primarily results from the gradual loss of epigenetic information - the instructions that regulate how our genes function.

Imagine your DNA as computer hardware and your epigenome as software. Throughout life, this software gradually becomes corrupted, leading to cellular dysfunction and the visible and invisible signs of ageing we experience.

Sinclair's supplement approach targets four main biological pathways:

1. Supporting NAD+ levels - This critical coenzyme naturally declines with age
2. Activating sirtuins - Proteins that help maintain DNA integrity and cellular function
3. Mimicking caloric restriction benefits - Without requiring severe dietary limitation
4. Enhancing cellular energy production - Through optimising mitochondrial function

🔬 The David Sinclair Supplement Protocol: Core Components

NMN (Nicotinamide Mononucleotide)

What it is

NMN serves as a direct precursor to NAD+ (Nicotinamide Adenine Dinucleotide), a vital coenzyme found in every cell that powers metabolism and supports DNA maintenance. If you're new to this compound, our guide on What is NMN? A Guide to Nicotinamide Mononucleotide provides a comprehensive introduction.

Why Sinclair takes it

Research shows NAD+ levels typically fall by approximately 50% between our 20s and 50s. Sinclair's extensive research into NAD+ has led him to believe that maintaining youthful levels could support various aspects of cellular health and longevity. To understand exactly How NMN Works in the Body, read our simple guide explaining the biological mechanisms.

Sinclair's dosage

In interviews and his podcast appearances, Sinclair has mentioned taking about 1 gram of NMN daily, typically divided between morning and evening.

The science

Laboratory studies with mice have demonstrated that NMN supplementation can boost NAD+ levels and potentially reverse certain aspects of cellular ageing. Human research, while still developing, shows promising early results for safely increasing NAD+ levels.

Key potential benefits include:

• Improved cellular energy generation
• Enhanced DNA repair capacity
• Activation of longevity-associated sirtuin proteins
• Support for healthy metabolic function

Wondering whether NMN is the right NAD+ precursor for you? Our comparison article NMN vs NR: Which NAD Precursor Is Better for Longevity? explores the differences between these popular compounds.

Resveratrol

What it is

Resveratrol is a natural polyphenol compound found in red wine, grape skins, certain berries and other plants. It first gained scientific interest as a potential explanation for the "French Paradox", the observation that French populations showed lower rates of heart disease despite consuming diets relatively rich in saturated fats. For a quick overview, check out our article Resveratrol: Everything to Know in 5 Minutes.

Why Sinclair takes it

Throughout his career, Sinclair has conducted extensive research on resveratrol's ability to activate SIRT1, a key sirtuin protein associated with longevity pathways. He considers resveratrol a "sirtuin activator" that works in partnership with NAD+ precursors like NMN.

Sinclair's dosage

According to his public discussions, Sinclair typically takes resveratrol in the morning, approximately 1 gram, accompanied by yogurt or another fat source to improve absorption.

The science

Early mouse studies produced promising results regarding longevity effects, though human research has shown more variable outcomes. Nevertheless, resveratrol has shown potential benefits for heart health, blood sugar regulation and brain function.

"Resveratrol and NMN work together like an engine and fuel. Resveratrol activates the sirtuins (the engine), while NMN provides the NAD+ (the fuel) needed for optimal function." — Based on Sinclair's frequent explanation

The synergistic effects of these two compounds are explored in detail in our article Live Longer, Feel Younger? NMN and Resveratrol Benefits.

TMG (Trimethylglycine or Betaine)

What it is

TMG functions as a methyl donor that supports vital methylation processes throughout the body. These biochemical processes influence numerous functions from gene expression to neurotransmitter production and detoxification.

Why Sinclair includes it

When supplementing with NAD+ precursors like NMN, the body consumes methyl groups during the conversion process. Adding TMG helps maintain adequate methyl group availability, potentially preventing imbalances in the body's methylation cycles.

The science

While TMG receives less attention in popular discussions than NMN and resveratrol, many longevity researchers consider proper methylation support essential when taking NAD+ precursors. TMG helps ensure the body maintains proper biochemical balance.

Why it matters

Proper methylation support may help prevent potential side effects from NAD+ precursor supplementation and supports overall cellular health.

For a deeper look at this complementary relationship, our article Can TMG and NMN Support Healthy Aging? explores the science behind this powerful combination.

💊 Additional Components in Sinclair's Regimen

Beyond his core supplements, Sinclair has mentioned several additional compounds in his personal protocol:

Vitamin D3 & K2

• Vitamin D3: 4,000-5,000 IU daily to support immune function and bone health
• Vitamin K2: 180-360 mcg to direct calcium properly to bones rather than arteries
• Testing: Sinclair monitors his levels with periodic blood tests

TMG (Trimethylglycine)

• Dosage: 500-1,000 mg daily
• Purpose: Supports methylation processes during NMN metabolism
• Rationale: Prevents depletion of methyl groups when taking NAD+ precursors

Lipoic Acid

• Dosage: Likely around 300 mg (standard dosage)
• Background: Sinclair conducted his PhD research on this molecule
• Benefits: Powerful antioxidant that supports cellular energy production

Spermidine

• Dosage: 1-2 mg daily
• Source: Naturally found in wheat germ, mushrooms and green vegetables
• Function: Activates autophagy, the cellular cleaning process

Fisetin

• Dosage: 500 mg taken with yogurt
• Category: Senolytic that helps clear senescent cells
• Benefits: Shows lifespan extension in animal studies

Fish Oil (Omega-3)

• Addition: Recently added to his regimen
• Benefits: Supports brain health and reduces inflammation
• Standard dosage: Many experts recommend 2g EPA and 1.5g DHA daily

L-Taurine

• Dosage: 2g daily
• Recent addition: Based on emerging research
• Benefits: Supports mitochondrial health and cardiovascular function

Prescription Medications

Sinclair also takes several prescription medications as part of his personalised approach:

• Metformin: 1g daily for metabolic health and potential longevity benefits
• Low-dose aspirin: 83 mg for cardiovascular protection and potential cancer risk reduction
• Statin (atorvastatin): For cholesterol management
• Rapamycin: Dosage unknown, taken for its effects on cellular maintenance pathways

🧪 The Synergistic Approach: How These Supplements Work Together

What makes Sinclair's protocol particularly fascinating is the potential synergistic relationship between the core components. This isn't simply a collection of random supplements but a carefully considered system where components complement each other.

The NAD+ and Sirtuin Connection:

1. NMN works to boost NAD+ levels that naturally decline as we age
2. Resveratrol helps activate sirtuins (particularly SIRT1), the proteins associated with longevity
3. Sirtuins require adequate NAD+ to function properly
4. Together, they create a complementary system supporting cellular health and function

This synergistic relationship explains why many people following Sinclair-inspired approaches take both NMN and resveratrol in combination rather than either compound alone.

Current scientific understanding suggests several key mechanisms:

• NMN serves as the primary "fuel" by boosting NAD+ levels
• Resveratrol functions as an "activator" that enhances sirtuin activity
• TMG supports the biochemical processes involved in NAD+ metabolism
• Together they create a comprehensive support system for cellular maintenance and repair
• This multi-target approach addresses several hallmarks of ageing simultaneously.

The practical impact:

Many people report that the combination produces more noticeable effects than individual components alone, though responses vary considerably between individuals based on genetics, lifestyle, age and other factors.

🥑 Beyond Supplements: Sinclair's Holistic Approach

It's essential to recognise that supplements represent just one element of Sinclair's comprehensive approach to longevity. His complete lifestyle regimen encompasses several key practices that work alongside his supplement protocol:

Intermittent Fasting and Time-Restricted Eating

Sinclair typically constrains his daily eating to an 8-10 hour window, often skipping breakfast entirely. Based on his research, this eating pattern helps trigger cellular cleaning mechanisms like autophagy (the body's process for removing damaged cellular components) and helps regulate metabolic health.

His typical approach:

• First meal around midday
• Last meal by early evening
• Occasional longer fasts (24-36 hours) several times yearly
• Emphasis on plant-rich foods during eating windows

Regular, Varied Exercise

Physical activity features prominently in Sinclair's personal routine and research recommendations. His approach typically includes:

• Resistance training 2-3 times weekly to maintain muscle mass
• Daily movement and steps (often using a treadmill desk)
• Cardiovascular exercise for heart health and mitochondrial benefits
• Brief periods of high-intensity training to create beneficial cellular stress

Plant-Forward Nutrition

While not strictly vegetarian, Sinclair advocates for a predominantly plant-based eating pattern:

• Abundant colourful vegetables and fruits for their polyphenol content
• Limited processed foods and refined carbohydrates
• Moderate protein intake from varied sources
• Limited alcohol consumption (though he acknowledges the potential benefits of compounds in red wine)
• Attention to specific "longevity-promoting" foods like olive oil, nuts, berries and leafy greens

Hormetic Stressors

Sinclair deliberately incorporates mild, beneficial stressors (hormesis) to activate cellular resilience:

• Regular sauna sessions for heat exposure
• Cold exposure through brief cold showers or plunges
• Variable temperature exposure to stimulate metabolic flexibility
• Moderate exercise intensity that challenges cellular energy systems

Comprehensive Stress Management

Mental wellbeing plays a central role in Sinclair's holistic approach:

• Regular meditation practice
• Prioritisation of quality sleep (7-8 hours nightly)
• Strong social connections and community engagement
• Purposeful work and cognitive stimulation
• Mindfulness practices integrated throughout daily activities

Implementing a Sinclair-Inspired Protocol

For those interested in incorporating elements of Sinclair's approach into their own routine, here's a practical roadmap to getting started on your longevity journey:

Build Strong Foundations First

Before investing in supplements, focus on establishing these fundamental lifestyle practices that Sinclair himself emphasises:

• Regular exercise: Aim for both cardiovascular exercise (like brisk walking, cycling or swimming) and strength training at least 3-4 times weekly. Sinclair particularly values resistance training for its impact on muscle preservation and metabolic health.
• Quality sleep: Prioritise 7-8 hours of uninterrupted sleep in a cool, dark room. Sinclair often discusses how proper sleep directly impacts cellular repair mechanisms and NAD+ levels.
• Stress management: Incorporate daily practices like meditation, deep breathing or mindfulness. Chronic stress accelerates cellular ageing through multiple pathways, including inflammation and telomere shortening.
• Nutrition optimisation: Adopt a predominantly plant-based diet rich in colourful vegetables and fruits. Sinclair typically follows a time-restricted eating pattern, consuming food within an 8-10 hour window.
• Hormetic stressors: Consider introducing beneficial stressors like sauna sessions, cold exposure or intermittent fasting that create mild stress to activate longevity pathways.

Follow a Measured, Strategic Approach

Rather than implementing the entire protocol simultaneously, consider this stepwise method:

Begin with lifestyle optimisations (3-6 months)

Establish consistent exercise, sleep, nutrition and stress management habits before adding supplements

Introduce core supplements individually (4-8 weeks between additions):

• Start with a lower dose of NMN (250mg daily) and assess tolerance
• Add resveratrol next if desired, beginning with 150mg daily
• Consider TMG third if using the other compounds
• Add complementary nutrients based on personal needs

Monitor your response systematically:

• Keep a simple journal tracking energy, sleep quality, recovery and cognitive function
• Consider periodic bloodwork to assess markers of inflammation and metabolic health
• Use wearable technology to track metrics like heart rate variability and sleep quality

Adjust based on personal results:

• Increase doses gradually if well-tolerated
• Be willing to reduce or eliminate components that don't agree with you
• Remember that personalisation is key—your optimal protocol may differ from Sinclair's

Re-evaluate regularly:

• Longevity science evolves rapidly
• Schedule quarterly reviews of your approach
• Stay informed about emerging research through reputable sources

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At Healthspan Formulas, we've developed a range of high-quality supplements that align with key components of Sinclair's approach to longevity. Looking for the best options available in the UK? Read our Best NMN Supplements 2025: Comprehensive UK Market Review for an unbiased analysis.

Nicotinamide Mononucleotide (NMN)

Our pharmaceutical-grade NMN provides 500mg per capsule in a delayed-release format for optimal absorption—the cornerstone molecule in Sinclair's longevity approach.

Key features:

• 500mg pure NMN per capsule
• Delayed-release technology for optimal absorption
• 60 capsules per bottle
• No unnecessary fillers or additives

NMN & TMG Complex

This comprehensive formula combines six key compounds featured in longevity research:

• NMN (β-Nicotinamide Mononucleotide)
• Trimethylglycine (TMG)
• Quercetin
• Pterostilbene
• Trans-Resveratrol
• Vitamin B12 (Methylcobalamin)

Longevity Essentials Bundle

The perfect starter kit featuring the two most researched compounds in Sinclair's work:

• 500mg NMN (60 capsules)
• 150mg Resveratrol (90 capsules)

This carefully calibrated combination mirrors the core supplementation approach discussed by Sinclair in his research and public communications.

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⚠️ Important Considerations and Limitations

When exploring any longevity protocol, it's essential to maintain perspective:

Ongoing Research Status

Much of the research on NMN, resveratrol, and other longevity compounds remains in relatively early stages, particularly in humans. While animal studies show promise, human evidence continues to evolve.

Individual Variation

Genetic factors, lifestyle, existing health conditions, and even gut microbiome composition can influence how individuals respond to various supplements and interventions.

Quality Matters

The purity, bioavailability, and overall quality of supplements can significantly impact their potential effectiveness. At Healthspan Formulas, we prioritise:

• Pharmaceutical-grade purity
• Optimised bioavailability formulations
• Rigorous quality testing
• UK manufacturing under strict standards

Not Medical Treatments

It's worth understanding that these supplements are not intended to diagnose, treat, cure, or prevent any disease. They're designed to support overall wellbeing as part of a comprehensive approach to healthy ageing.

Conclusion: A Personalised Approach to Longevity

David Sinclair's pioneering research has transformed how we understand ageing. Rather than viewing it as inevitable decline, his work suggests ageing is a biological process that can potentially be influenced through targeted interventions.

While scientific understanding continues to evolve rapidly, the core principles remain: supporting cellular health, enhancing energy production, maintaining DNA integrity, and activating longevity pathways.

The most important insight from Sinclair's work is the emphasis on personalisation. Each person's optimal approach will vary based on genetics, existing health conditions, age, lifestyle and numerous other factors. Ideally, this journey should be undertaken with guidance from healthcare providers knowledgeable about integrative and longevity medicine.

Whether you're a longstanding follower of Sinclair's research or just beginning to explore evidence-based approaches to healthy ageing, our premium formulations provide the purity, potency and proper combinations to support your personal longevity journey effectively.

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