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David Sinclair: The Science of Keeping The Brain Healthy

Updated: Jan 16

Released Date: 2/15/22

Podcast Duration: 1:02:08

5 Key Takeaways

  1. Sleeping for 7-8 hours per day will increase brain function and slow aging

  2. Eat a diet that is rich in Omega 3 fatty acids, at least 1 gram per day

  3. Continue to learn new things to improve neural plasticity and reduce brain aging

  4. Taking an NAD supplement may improve longevity

  5. Exercise daily to support blood flow to the brain

In this episode, Dr. David Sinclair discusses brain aging with co-host Matthew LaPlante. They examine evidence around the idea that the brain ages more slowly than other parts of the body and discuss how aging impacts cognitive function. In addition, a plant-based diet, exercise, metformin, NAD boosters, and sufficient sleep are discussed as ways to preserve brain health.

Ex-differentiation as a Driver of Aging

  1. A new idea of aging is that it's not just random variables going wrong, there is actually a program that begins at birth

  2. During birth, and prior to that is when cells gain an identity

  3. Epigenome is the regulator of the genome (series of DNA that tells the body what to do)

  4. Aging is like scratches on a CD and you cannot read the right songs at the right time

  5. A brain cell over time starts to play the "music" of a liver cell or a skin cell and doesn't function correctly

The Brain Ages Slowly

  1. The Brain Age is slower than the rest of the body in early life

  2. There is a very good chance that your brain is biologically younger than you are

  3. Predicted age is lower in the brain than anywhere else in the body, sometimes just a quarter of the age of other parts of the body

  4. Our brain is protected by a blood brain barrier, it doesn't get hit by UV light, like our skin does

  5. The blood brain barrier prevents toxins from the blood to enter into the brain

  6. These super protective mechanisms keep the brain stay younger for longer, but they're not perfect

  7. By working on aging we can keep the whole body young, including the brain

  8. The volume of the brain after the age of 40, reduces about 5% per decade

Cognitive Function and Plasticity

  1. We live in a world now where every year you have to be learning something new

  2. A plastic environment is an ever changing environment

  3. We need plasticity (the brain learning new things) to respond to these changes over time

  4. You'll be isolated if you are not able or willing to adopt new changes to your environment

  5. This requires a brain that is highly adaptable

Three Longevity Pathways: mTOR, AMPK, and Sirtuins

  1. There are three main buckets of longevity factors that respond to adversity

  2. mTOR plays in autophagy (the removal of dysfunctional cells)

  3. Sirtuins are central to brain health

  4. Sirtuins respond to a whole variety of environmental pseudo stressors

  5. They make cells more resistant to toxins and stress

  6. Cert 1 is most important for controlling brain aging

  7. AMPK helps to stimulate energy generating processes

  8. Brings more ATP(energy) to cells so they can function more efficiently

Plant-based Diets and B-vitamins

  1. The Mediterranean type diet protects the brain from aging and can even reverse aspects of aging

  2. There was a 10% reduction in dementia risk for people on the Mediterranean diet

  3. That includes olive oil in the diet, red wine, and not a lot of red meat

  4. Resveratrol from red wine has clearly been shown to be beneficial in enhancing metabolic and brain efficiency

  5. Also reduces cancer risk

  6. Plant based diets have low levels of animal proteins

  7. This tricks the body into thinking that the food supply is limited

  8. Stimulates hormesis (makes cells more adaptable and resistant to disease)

  9. If you're just consuming plants, a deficiency in folic acid (vitamin B-9) and cobalamin (vitamin B-12) is likely

  10. These B vitamins contain metals that are added and subtracted from the DNA

  11. This controls the DNA methylation clock (predicts biological age)

  12. If you have low levels of B 12 then it is very likely to accelerate the clock in a way that causes aging

Homocysteine, Plaque, and Vasculature

  1. High homocysteine levels are a predictor of heart disease and dementia

  2. Lack of B vitamins raises these levels

  3. The best way to keep homocysteine levels low is to make sure B-12 levels are optimal

  4. High homocysteine levels do correlate with increased susceptibility to plague build up in arteries

  5. This leads to decreased blood flow in the vasculature (arteries and veins)

Fatty Acids

  1. The majority of Americans do not get enough omega three fatty acids (anti-inflammatory)

  2. Fish, Salmon,Mackerel, Krill, and Sardines are good sources of Omega 3s

  3. There are three main sources of Omega 3s

  4. EPA- Eicosapentaenoic acid

  5. EPA is the most important one and you want to get at least a gram of that per day

  6. DHA- Docosahexaenoic acid

  7. ALA- Alpha linolenic acid

  8. If you follow a plant based diet it is important to supplement this fatty acid

  9. You can get ALA from flaxseed, walnuts, chia seeds, and linseed oil

  10. Omega threes actually form a structural component that protects the brain from inflammation

Physical Activity

  1. Aerobic exercise (cardio) such as walking will improve your chances of having a better memory and cognition as you get older

  2. There are two reasons why exercise improves longevity

  3. Better blood flow

  4. Improved neuronal activity which slows aging of brain cells

  5. Exercise can greatly improve executive function (working memory, flexible thinking and self control)

  6. Strength training can increase the level of factors that grow new brain cells and optimize nerve pathways


  1. This drug was originally created to treat type II diabetes

  2. Lowers blood sugar levels

  3. Different studies on fish, mammals and humans show that Metformin is good for brain health

  4. Taking metformin increases mitochondrial hormesis which will raise NAD levels

  5. This increases energy availability to the cell

  6. Studies show that Metformin can reduce dementia incidents by 55%

NAD Boosters

  1. There has been a lot of animal research on NAD boosters which show that it can elevate cognitive functioning and promote recovery after brain injury

  2. NAD levels go down for a couple of reasons

  3. Poor diet

  4. Lack of exercise

  5. Stress

  6. NAD activates sirtuins in a test tube and in the cell

  7. NR which is another kind of NAD booster that slows down the progression of ALS

  8. More research needs to be done to determine the effectiveness of NAD boosters in humans

Increasing Blood Flow

  1. Vascular (blood) flow is important in our bodies and even more important in our brains

  2. Our brain requires blood flow and oxygenation to function properly

  3. NAD boosters may improve blood flow which results in vascular flow increase

  4. A study shows that overexpression from NAD turned up cert 1 in the brain, extending a mouse's lifespan

  5. This protects them against ALS, Huntington's and Alzheimer's disease


  1. Research shows if you don't sleep you're going to age faster

  2. Cert 1 and NAD play a fundamental role in controlling your wake sleep cycle

  3. Sleep efficiency actually declines with age

  4. Try to get sunlight early in the morning

  5. This provides a natural energy boost

  6. Helps reset circadian rhythms

  7. NAD boosters can improve symptoms in human subjects suffering from sleep deprivation

  8. Our brains are being besieged with stress all the time, we need sleep to reset

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