Lifespan with Dr. David Sinclair

Episode 2: What to Eat & When to Eat for Longevity

Date: January 12, 2022
Hosts: Dr. David Sinclair, Matthew LaPlante

Overview

In this episode, Dr. David Sinclair and co-host Matthew LaPlante dive deep into the science of when and what to eat to maximize healthspan and longevity. They break down the biological mechanisms behind fasting, eating frequency, and dietary choices, sharing personal experiences, landmark studies, and practical, science-backed tips for listeners to optimize their eating patterns. The conversation covers intermittent fasting, calorie restriction, timing, the role of specific nutrients, and the benefits of plant-based foods—all presented with Sinclair’s trademark enthusiasm for self-experimentation and data-driven decision making.

Key Discussion Points and Insights

The Core Principle: Eat Less Often

• Sinclair’s lifelong advice for longevity:
  “Eat less often. That is the one thing that'll have the biggest impact on your longevity.” – Sinclair [05:03]
• Eating less often is more important for longevity than simply reducing calories [05:09]
• Fasting periods trigger “body defense” mechanisms that promote longevity—even in overweight individuals, though optimal weight matters [06:04–06:43]
• Weight loss is a common side effect of eating less often, and studies show being lean is associated with longer life [06:59]

The Science Behind Fasting and Calorie Restriction

1. Universal Longevity Mechanism

• Research shows calorie restriction extends lifespan across yeast, worms, flies, mice, and dogs [08:20–09:12]
  • Ex: Labradors’ lifespan increased by 1.8 years with 25% fewer calories [09:12]

2. Sirtuins: Key Longevity Genes

• Sirtuin genes get activated under low energy (calorie restriction); they protect DNA and the epigenome [08:50–12:16]
• Boosting sirtuins via NAD fuel—either naturally through fasting or with supplements—improves cell health [12:16–13:58]
• “We found that if we deleted that sirtuin gene in the yeast... then caloric restriction in the yeast didn't work anymore, which... told us that this wasn't just glucose being bad for you.” – Sinclair [14:36]

3. MTOR & AMPK Pathways

• MTOR: Downregulated by fasting or low protein; triggers autophagy to clear out damaged proteins, important for longevity [15:35–16:37]
• AMPK: Rises with hunger/low energy; stimulates new mitochondria, improving energy and anti-aging [16:48–17:28]
• All three pathways (Sirtuins, MTOR, AMPK) work together to signal scarcity and repair mechanisms in cells [18:42]

4. From Lab Animals to Humans

• While most data come from animal models, clinical trials with humans using fasting-mimicking drugs (metformin, rapamycin) show promise for slowing aging and reducing disease [19:20–21:14]
  • “Just those facts ... make me convinced that fasting and the drugs that mimic fasting are going to be important for long term health.” – Sinclair [20:56]

Traditional & Modern Fasting Practices

• Long-lived human populations, like the Jains of India, have religious fasting traditions and experience excellent health outcomes [21:57–22:20]
• Similar observations with Christians, Muslims, and other cultures [22:11, 22:20]
• Scientific studies (e.g., dawn-to-sunset fasting for four weeks) show improvements in blood pressure, BMI, waist circumference, and DNA repair in humans [23:28]

Understanding Different Fasting Regimens

Listener Guidance:
“You’re an individual... What we're saying is you can try this. If it doesn't work for you, try something else.” – Sinclair [25:30]

• Fasting-Mimicking Diet: (Valter Longo’s protocol) lowers MTOR through restricting specific amino acids [27:21]
• Intermittent Fasting (IF): Going without food for ≥24 hours; deepsters activate intense autophagy (“deep cleanse”) after 3 days [27:45]
• Time-Restricted Feeding (TRF): Most accessible—e.g., eating only within an 8-hour window, fasting for 16+ hours [28:58]. Sinclair shares he eats one main meal (dinner) [30:00]

Tips for Implementation:

• Ramp up: Start by skipping one meal (usually breakfast) for 2 weeks, then try skipping both breakfast and lunch; adaptation takes 2–3 weeks [32:04]
• Symptoms (hunger, brain fog) often disappear with adaptation [31:39, 33:17]

Self-Experimentation and Monitoring

• Measure Your Response: Use personal biomarkers (like those from InsideTracker) and continuous glucose monitors to assess what works for you [26:31, 33:21]
• Different foods affect individuals differently (e.g., Sinclair reports white rice and grapes spike his blood sugar; potatoes don't) [33:29, 34:14]

Practical Fasting Tips

• Stay hydrated with water, coffee, or tea to curb hunger [37:08]
• If you must eat, a handful of nuts can suppress hunger pangs [37:29]
  • “Being hydrated and filled with liquid takes away any feeling of hunger. Also, nuts... take away the feeling of hunger rapidly.” – Sinclair [37:08–37:29]

Intermittent Fasting with Adequate Nutrition (“IFAN”)

• “The acronym would be IFAN... Intermittent Fasting with Adequate Nutrition.” – Sinclair [39:02]
• Supplement with micronutrient-dense foods or greens powder to avoid deficiencies [39:32–39:51]

What to Eat (and What to Avoid) for Longevity

Eliminate or Greatly Reduce Added Sugar

• “The big killer is sugar. Glucose, particularly fructose, is also pernicious.” – Sinclair [40:36]
• Excess sugar causes protein glycation, diabetes, cardiovascular disease, suppresses key longevity genes, and creates ‘brain fog’ [41:07–42:06]

Rethink Daily Protein, Especially Animal-Based

• Avoid chronically high protein/meat diets as they keep mTOR and sirtuins switched off [42:59–44:10]
• Plant-based proteins are adequate, and plant aminos are less bioavailable, making your body “work harder”—a good thing for longevity [44:20]
• Sinclair is now mostly vegetarian, noting the benefits and sharing his evolving experience [44:52–44:57]

Plant-Based and Mediterranean Diets

• The Adventist Health Study (2013) shows stepwise reduction in mortality as diets become more plant-focused (“hazard ratio” for pesco-vegetarian: 0.81 = 19% lower risk of death) [48:16–49:39]
• Mediterranean diet—rich in plants, olive oil, little fish/meat, and some wine—significantly reduces biological aging and death risk (studies support 31% reduction in mortality if adopted before age 80) [50:01–61:25]
  • “If you're under 80 and you do [the Mediterranean diet], you reduce your mortality... by 31%.” – Sinclair [61:25]

Stress-Resilient (“Xenohormetic”) Plants

• Plants produce beneficial polyphenols (like resveratrol) under stress—found in organically grown, colorful, sometimes “imperfect” produce and in wines like Pinot Noir [54:51–58:07]
• “We need to put our bodies in a state of want for them to fight diseases and have ultimate health in old age.” – Sinclair [66:35]

Notable Quotes & Memorable Moments

• Sinclair, on fasting for longevity:
  “What we're going to remember is the period of not eating that's so important for boosting the body's defenses against aging to maximize longevity.” [06:04]
• On glucose:
  “Glucose isn’t bad for you, but not for the reason that you might think.” [15:09]
• On self-experimentation:
  “We should ban bathroom scales if we're not allowed to measure our body.” – Sinclair, defending personal health tracking [35:46]
• On adaptation:
  “Do it for at least two weeks... your liver has now learned that you're not going to have breakfast or lunch and it will start making glucose at a steady level.” [31:39]
• On eating order:
  “There’s even an order which you can eat your meals to reduce the blood sugar spike... put the sugar at the end of the meal, so dessert is fine, but put it at the end.” – Sinclair [63:06]
• On modern diets:
  “We have this metabolic winter hypothesis... we lived cold and hungry. These days, we live in air conditioned and heated houses with food always available, which goes against what we've evolved to be optimal.” [65:44]
• On the impact for children:
  “What we do to kids is we say, big breakfast, here's a snack, here's a lunch... big dinner, go to bed, full, wake up, eat some more... and we're also setting them up for obesity, which shuts off their survival programs right now.” – Sinclair [63:53–64:54]

Timestamps for Major Segments

• Eat Less Often: [04:56–06:43]
• Fasting Mechanisms (Sirtuins, MTOR, AMPK): [08:20–18:42]
• Fasting in Human Populations & Clinical Evidence: [21:14–24:42]
• Popular Fasting Regimens & Practical Tips: [25:24–39:51]
• What to Eat (Reduce Sugar & Meat, Plant-Based Focus): [40:36–44:52]
• Blue Zones, Mediterranean, Okinawan Diets: [47:43–53:37]
• Xenohormesis & Stressed Plants: [54:07–58:07]
• Recap & Practical Checklist: [58:07–63:06]
• Impact on Children & Societal Eating Patterns: [63:41–66:35]

Checklist & Actionable Takeaways

1. Eat Less Often: Start by skipping breakfast, then consider skipping lunch (time-restricted feeding, aiming for ≥16 hours of fasting).
2. Don’t Snack: Avoid grazing and mindless eating.
3. Minimize Added Sugars: Especially from sweetened drinks, treats, and processed foods.
4. Reduce Red/Processed Meat: Move toward more plant-based options, fish if desired, and emphasize plant proteins.
5. Eat Stress-Resilient Plants: Organic, colorful, local produce; enjoy “imperfect” and wild foods; consider some red wine.
6. Sequence Your Meals for Lower Glucose Spikes: Save carbohydrates/sugar for the end of meals.
7. Monitor Your Body’s Signals: Use tracking tools or periodic bloodwork to personalize your approach.
8. Teach and Model Healthy Patterns for Children: Allow hunger between meals to foster resilience and healthier biology.
9. Remember: It’s never too late to make a difference—even changes in your 70s and 80s are beneficial.

Closing

Dr. Sinclair and Matthew LaPlante emphasize that the science of longevity is evolving, but the core message is robust: periods of scarcity (fasting) and a focus on plant-based, nutrient-dense foods maximize our bodies’ natural defenses, reduce disease risk, and may even reverse the biological clock. Next episode: how cold exposure, exercise, saunas, and other stresses confer similar benefits.