Saturday, January 28, 2023
Mitochondrial Health

The Science of Keeping the Brain Healthy | Lifespan with Dr. David Sinclair #7

In this episode of the Lifespan podcast, Dr. David Sinclair and co-host Matthew LaPlante dissect the topic of brain aging. They explore evidence suggesting that the brain ages more slowly than other parts of the body and highlight how cognitive function is impacted by aging. Different interventions aimed at preserving brain health are also discussed, including a plant-based diet, exercise, metformin, NAD boosters, and sufficient sleep.

#DavidSinclair #Longevity #BrainHealth

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00:00:00 Introducing Episode Seven: Aging of the Brain
00:04:39 Thanking the Sponsors
00:07:38 Ex-differentiation as a Driver of Aging
00:09:22 The Brain Ages Slowly
00:14:17 Cognitive Function and Plasticity
00:17:44 Three Longevity Pathways: mTOR, AMPK, and Sirtuins
00:23:26 Plant-based Diets and B-vitamins
00:28:32 Homocysteine, Plaque, and Vasculature
00:32:35 Fatty Acids
00:35:48 Physical Activity
00:39:14 Metformin
00:46:02 NAD Boosters
00:50:33 Increasing Blood Flow
00:53:20 Sleep
00:58:02 Overall Message: Keep your Brain Healthy
00:58:50 Next Week’s Episode and the Future of Medicine
01:01:21 Options for Subscription for Support

The cerebellum in the brain ages slowly:
Neuronal cells have a lower epigenetic age:
Sirt1 regulates aging in mice:
Mediterranean diet and brain health:
Mediterranean diet and dementia risk:
Aerobic exercise improves executive functioning:
Exercise and mouse models of neurodegenerative disease:
Strength exercises elevate the expression of BDNF:
Metformin enhances cognitive ability in fish:
Alzheimer’s disease and metformin:
Metformin use correlates with a reduced risk of dementia:
NAD boosting and Alzheimer’s disease:
ALS, nicotinamide riboside, and pterostilbene:
Vascular aging and NAD in mice:
In mice, overexpressing Sirt1 in the brain extends lifespan:
Sirt1 ameliorates amyotrophic lateral sclerosis in mice:
Sirt1 protects against Alzheimer’s disease in mice:
Sirt1 and neuroprotection in a mouse model of Huntington’s disease:
Sleep loss reduces lifespan in flies:
A single night of sleep deprivation increases amyloid-beta:
All-cause mortality correlates with sleep duration:

Please note that Lifespan with Dr. David Sinclair is distinct from Dr. Sinclair’s teaching and research roles at Harvard Medical School. The information provided in this show is not medical advice, nor should it be taken or applied as a replacement for medical advice. The Lifespan with Dr. David Sinclair podcast, its employees, guests and affiliates assume no liability for the application of the information discussed.

Title Card Photo Credit: Mike Blabac –

Special thanks to our research assistants, Adiv Johnson & Sarah Ryan.


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44 thoughts on “The Science of Keeping the Brain Healthy | Lifespan with Dr. David Sinclair #7
  1. I've been listening to you and am amazed at all research and trials that you have been conducting for the benefit of mankind. Sitting here in India I am able to get the information that I would never have access to. Thank you for all your talks. My question to you is, I have been doing intermittent fasting and loving it. I did it for a month with great results, high energy levels. However I was taking no supplements. I am again on intermittent fasting for the past one month. Two meals a day and I have just been diagnosed with a vit B deficiency. I have started on a vit B supplement. Do you have any suggestions on what I should do. Thanks. Looking forward to hearing from you.

  2. Getting metformin is almost impossible in the uk and maybe also in other countries its very hard, or impossible – unless you have diabetics or are a famous person who seem to be able to bypass the doctor training system. Is there an alternative ?

  3. Thank you guys so much for doing what you do! It’s really mind opening learning from you Mr. Sinclair.

    I have one question that you may be able to shed some light on. Is any kind of intermittent fasting acceptable if one is missing their gallbladder?

  4. Resveratrol from red wine – you mentioned in a previous podcast that one glass of red wine per day has such small amounts of this that it makes it inconsequential, and that you would need to drink thousands of glasses of red wine to have any real meaningful result perhaps over the course of years. Is the benefit higher than the liver damage, or potential psychological addiction to alcohol? Wouldn't taking a supplement or perhaps finding a less damaging source of resveratrol be more beneficial?

  5. I think photobiomodulation as well as Ubiquinol with PQQ taken with something like Thorne’s ResveraCel all complement the mitochondrial ATP / NAD / Sirtuin pathways.

  6. I used cassette tapes in my 1996 vehicle until 2011 when I got my first vehicle with a cd 💿 player. I just started pairing devices for music in 2020. Lol I guess I've been sleep 😴 💤 😅 😴

  7. The “Lifespan” book and these 8 videos are amazing breakthrough information sources on options for optimal health and good health as we age. Am so grateful to Dr. Sinclair and Matt for your high quality and accessible information. At age 72, I have been a consumer of supplements since age 20, exercise (have been physically active all of my life), intermittently fast, adjust my diet as age and information indicate what may be best. Have always looked younger than my actual age. But now am experiencing a “slowing down” that shows up as less physical energy and cognitive changes that are…potentially concerning.
    Now I am motivated to find a doctor who is interested in good health at an older age and can assist me in a balanced and helpful way.
    While exploring the various supplements and drugs talked about in the series, I have found it challenging to know the quality of supplement sources for NMN, Resveratrol, and others. It appears that buying NMN in bulk is a good option. And I understand that voicing your sources for these supplements would cause all kinds of unintended consequences. But I sure would love to know your best sources for these supplements and drugs.
    Thank you Dr. Sinclair and Matt!!! So grateful for all your good work.

  8. Hi Guys! Another great episode and I thank you for that. There's great knowledge being produced and leveraged against the onset, progression of, and actual regression of Alzheimer's symptoms being done by UCLA neurologist Dr. Dale Bredesen. He and his team have discovered 30 factors that will contribute to the onset of the disease, and most importantly, have proven that when these "insults" to the body are removed- the progression of the disease is reversed and in some cases is actually cured. Amazing work that has been duplicated hundreds of times to the point that his team has now trained over 2000 healthcare practitioners in doing this for their patients across the country and the world.

  9. Thank you David and Mathew for an excellent series. Apologies if this was corrected later in the podcast, I didn't want to forget posting this. There is a slight error earlier on – vitamin B12 refers to the cobalamins not to folic acid. B12 is found only in animal products and faecal matter contaminated vegetables. There is some synthesis by bacteria in the large bowel, and some evidence of absorption, although I'm not aware of this being quantified. Folic acid is the term for synthetic folate, which is distinct from naturally occurring folates. Folic acid is in an oxidised form and needs to be converted to be biologically active, whereas natural folates in food are in their oxidised form. Folate, sometimes referred to vitamin B9, but not frequently, is mostly found in plants, although liver, being the storage organ, is also a viable source. I look forward to listening to the rest of the podcast.

  10. I recently read viagra reduces Alzheimer’s by 70% and it could be to do with increased blood flow. If you ever do brain health update video it would be nice to touch on viagra. Thank you

  11. As an extremely busy professional and getting a little older, I enjoy learning about avenues that could help keep me optimizing my overall function/performance. Great podcast and the 2 hosts work really well together.

  12. My homocysteine levels been high since I decided to test it. I got it once down to normal, only once. All I have found is that it is affected by B12 and folic acid.
    Can you help me to lower it?

  13. I hope this podcast becomes a perfect example of the cart leading the horse. If people are primed to expect research and results, I think they're more likely to advocate for it. All of these happy futures can only be achieved if we fund them. And funding is driven by interest.

  14. Hi, with regards to bloods I have heard you speak about 7 main biomarkers to check (on the Andrew Huberman podcast), but please would you kindly list what these biomarkers are. Many thanks.

  15. I would like to hear David talking about the studies that say that resveratrol is not doing what David says in the body just works in co trolled environment in petri dish was kind of disappointing to hear that resveratrol is not good for what David says

  16. I see that David Sinclair has posted a video and come directly to give it a like, even before I watch it.That is how good everything he does is. Thank you sir.

  17. A futuristic movie made in 2005 called 'The Island' with Ewan McGregor & Scarlett Johanssen had a scene where Ewan (with the single prick of his finger each morning) had his blood analyzed and was told what to eat that day. Island Tracker seems something like that, but not as simple. 🙂

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