Episode 7: The Science Of Keeping The Brain Healthy | Lifespan With Dr. David Sinclair

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Key Takeaways

  • The paradox of living longer: our brain ages slower than the rest of our body but because modern medicine has helped us live longer, more people are living with cognitive decline, Alzheimer’s and dementia
  • The average onset of dementia is 80 years old but on average, the volume of the brain decreases about 5% every decade after the age of 40
  • The eyes are a window to the brain: keep up with eye health and ophthalmology visits!
  • Maintaining the right ratio of EPA:DHA can help improve memory and counteract depression (men target 1.6 grams, women about 1.3 grams)
  • It’s a good idea to supplement with 1g of omega-3 fatty acids daily, particularly if on a plant-based diet (of course, talk to doctor first)
  • Nutrition tips for a healthy brain: (1) follow a Mediterranean diet or variation of a diet with less meat; (2) if following a plant-based diet consider supplementing B6, B3, omega 3s, DHA, EPA; (3) keep blood sugar in check
  • Exercise doesn’t just make you feel better, you’ll think better
  • “As you get older you lose your ability to sleep, and if you don’t sleep well you’ll lose your ability to fight aging.” – Dr. David Sinclair


Dr. David Sinclair is a biologist, professor of genetics at Harvard, author, and expert on aging and longevity. His research and biotech companies focus on understanding why we age and how to slow its effects.

In this episode of Lifespan, David Sinclair & Matthew LaPlante breakdown aging and the brain. They review evidence related to the speed at which the brain ages, highlight the effects of aging on cognitive function, and behavioral and lifestyle interventions for optimal brain health.

Host: David Sinclair (@davidsinclair)  Co-Host: Matthew LaPlante (@mdlaplante)

Horvath Aging Clock

  • Horvath Aging Clock: most accurate molecular measure of chronological age – applies to all cells with DNA, tissues, organs, prenatal samples, super-centenarians (100+ years of age)
  • Collected through DNA sample and accurately estimate chronological age
  • People age at different rates as evidenced by biomarkers
  • Some appear older or younger than chronological age
  • “Biologic age” relates to morbidity and mortality risk in addition to aging but is not well defined
  • Depending on how you measure biologic age you get different answers – i.e., maybe you’re only looking at glucose levels which are high but methylation is normal

Aging & The Brain

  • Modern medicine has been keeping the body healthy longer, but more people are living with dementia and cognitive impairment because of how many years we are alive
  • The neurological biological clock is ticking all the time – what you do in your 20s and 30s impacts cognition and aging later in life
  • Cognitive decline isn’t just a disease of late stage life – it begins in middle age
  • The new theory of aging, ex-differentiation of cells: there’s not just a breakdown of lots of random things over time, but instead that cells are programmed at birth and given specificity
  • The brain does not ex-differentiate at the same pace as other cells in the body so ages significantly slower than the rest of the body – possibly in part because of the natural protection of the brain (i.e.,not exposed to UV lights and as many toxins)
  • By keeping the body young, we can help keep the brain healthy
  • For most of our history, we didn’t need sophisticated education function later in life but we were rarely living long enough for it to matter
  • Nowadays you really can’t be an older person and adopt new changes to environment and technology or you’ll be isolated – we need a healthy brain later in life

Longevity Pathways

  • Adversity mimetics: things that mimic biological adversity that is conducive to better lifespan and healthspan
  • Adversity signals survival circuit and turns on specific survival genes
  • Three longevity pathways/adversity mimetics: (1) mTor – senses levels of amino acids in the cell; (2) AMPK – senses energy/glucose; (3) sirtuins – sense NAD
  • All three adversity mimetics work together – sirtuins activate AMPK, AMPK can activate sirtuins and mTor
  • mTor mobilizes proteins to be recycled and made into new proteins (AKA autophagy)

Lifestyle Factors To Optimize Brain Health

  • Mediterranean diet: extensive research has shown that the Mediterranean diet can protect against aging in the brain and even reverse some signs of aging in the brain
  • Related articles: Mediterranean Diet And Brain Health and Mediterranean Diet And Dementia Risk
  • Mediterranean diet components: olive oil, red wine, not too much red wine
  • Why does the Mediterranean diet work? resveratrol in wine, oleic acid from olive oil can activate enzymes, xenohormetic molecules in plants
  • Plant-based and plant-heavy diets with low levels of protein trick the body into thinking food supply is low and could run out
    • Tips for proper nutrition on a plant-based diet: supplement with folic acid and vitamins B6 and B3 which build up NAD for sirtuins (options for vitamin B6 and B complex with folate)
  • Low levels of B12 can cause deficiency and errors in DNA methylation which can accelerate heart disease, dementia, and general clock
  • Importance of fatty acids: omega-3s are the building blocks to the brain – if you aren’t eating enough fish, consider supplementing to achieve proper ratios of omega-3:EPA:DHA
    • Men need about 1.6 grams of ratio EPA:DHA and women need about 1.3 grams
  • The brain needs fat to protect the brain from inflammation and damage
  • Food sources of omega-3: salmon, mackerel, krill, sardines
  • People on plant-based diets get omega-3s from alpha linoleic acid (ALA) which is converted by the body to EPA and DHA – food sources: flax seeds, chia seeds, seaweed
  • The importance of exercise: aerobic exercise and walking improve cognition, particularly as we age
  • Find an exercise you like! It’s never too late – it’s more important than ever to exercise later in life

The Role Of Supplementation, NAD, And Sirtuins For Brain Health

  • High blood sugar is bad for brain activity and really, leads to dysfunction in all tissues
  • Metformin has had good success in improving brain health – even improving executive function (ability to focus) in patients with mild dementia
  • Some studies have shown a reduction in onset of dementia by 55%
  • The role of sirtuins is to repair the structure of epigenome
  • Relationship between sirtuins & NAD: sirtuins create bundles of DNA and create its identity so the genes can be read properly – NAD activates sirtuins
  • As we age, we make less NAD and burn more of it – supplementing a healthy diet and exercise regimen with an NAD booster can slow the clock
  • Taking 250mg of nicotinamide riboside (NR) daily will likely increase NAD and decrease inflammation, but changes in body composition and mitochondria are debatable in humans
  • Nicotinamide mononucleotide (NMN) seems to be more effective than NR at improving vascular tissue, enhancing insulin sensitivity, and seems promising for slowing aging but further studies need to be done
  • Sirtuins in the brain: (1) turning up sirtuins in nerve cells of the brain extends mouse lifespan; (2) activation of hippocampus by sirtuins or resveratrol improves memory in old age mice


  • The hypothalamus controls the circadian rhythm
  • Sirtuins and NAD increase in the morning to wake up you and decrease at night to prepare you for sleep
  • If you lose the function of sirtuins and NAD, not only will you lose sleep – you will age poorly
  • “As you get older you lose your ability to sleep, and if you don’t sleep well you’ll lose your ability to fight aging.” – Dr. David Sinclair
  • Get light early in the morning to wake your system and help regulate your natural sleep cycle
  • Options for sleep supplements: NMN (not currently over the counter), magnesium, theanine   
  • If you restrict rats from sleep, previously healthy rats get diabetes within 2 weeks
Lifespan With Dr. David Sinclair : , , , ,
Notes By Maryann

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