All three pathways play a role in autophagy (cleaning out damaged cells), but mTOR is the most potent. mTOR responds to insulin signalling and fasting. In response, it mobilises proteins to be recycled and made into new proteins when you’re hungry.  When we get older, we have misfiled proteins: In the eye, they’re called lipofuscin. In Alzheimer's, they’re plaques and tangles of proteins. To get rid of them, you need deep cleansing called chaperone-mediated autophagy.Changing our diet ensures all three pathways are working.

Autophagy

<ul><li>mTOR, responds to low amounts of amino acids, particularly leucine, isoleucine, valine.</li><li>AMPK pathway. AMPK senses low energy, low glucose levels, and makes more energy, more mitochondria, boost NAD.</li><li>Sirtuins. The sirtuins require a fuel called NAD that can be activated by certain chemicals. As we age, we make less NAD and burn more of t.</li></ul>All three factors work together to protect the body. They turn up metabolism, burn fat, repair DNA, remove senescent cells, they lower inflammation.

Three main longevity factors that respond to adversity

A good Mediterranean-type diet protects the brain from ageing and can even reverse aspects of ageing in the elderly. A Mediterranean diet includes olive oil in the diet, red wine, and very little red meat.<ul><li>Red wine has polyphenols that directly activate SIRT1.</li><li>Olive oil has oleic acid, which is also found in avocados and can also directly activate the enzyme.</li><li>Low levels of protein and a plant-based diet.</li></ul> The Mediterranean diet mimics adversity. Your body has to work a bit harder to get everything it needs.  Aerobic exercise and walking improve cognition, particularly as we age.

Diet and Exercise

<ul><li>High blood sugar is bad for brain activity and leads to dysfunction in all tissue.</li><li>Metformin has had good success in improving brain health.</li><li>Taking 250mg of nicotinamide riboside (NR) daily will likely increase NAD and decrease inflammation.</li><li>Nicotinamide mononucleotide (NMN) seems to be more effective than NR at improving vascular tissue</li></ul>

Other supplementation

Dr David Sinclair is a professor of genetics at Harvard, a co-director of the Paul F Glenn Centre for Biology of Aging Research, and an author. His research and biotech companies focus on understanding why we age and how to slow its effects.

Dr David Sinclair's introduction

The new idea of ageing is that it’s not just random stuff in your body going wrong. There’s actually a program that starts at birth. The Horvath clock or epigenetic clock is the biological clock that is ticking all the time. The clock is measured by the methylation of the DNA. A chemical called methyl is added to the DNA and it stays there and ensures that cells have their identity and play the right genes for the rest of your life.  What you do in your 20s and 30s will impact how healthy you are in your 70s, 80s, and 90. There are ways to work on ageing that can keep the whole body young.

Why we age

The brain age ages slower than the rest of the body. The brain has super protective mechanisms that keep the brain younger for longer.  After the age of 40, the volume of the brain reduces about 5% per decade. However, you can slow that process down and even reverse it later in life.

The brain ages different to the body

<ul><li>If you eat a plant-based diet, supplement with vitB12, B6 and B3. These B vitamins ensure you have the methyls that control the DNA methylation clock.</li><li>Low levels of B12 can cause deficiency and errors in DNA methylation and can accelerate heart disease and dementia.</li><li>Omega-3s are building blocks of the brain. If you don't eat enough fish, consider supplementing to achieve proper ratios of omega-3: EPA:DHA.</li><li>The brain needs fat to protect the brain from inflammation and damage.</li></ul>

B vitamins and omega 3s

While your body clock is ticking away, the loops and bundles of the DNA are getting messed up. When a cell is overstressed and damaged, the sirtuins have two jobs:<ol><li>They have to make bundles of DNA and ensure the cell has its identity. When the chromosomes break or you crush a cell, the sirtuins rush in to help repair the broken DNA.</li><li>Sirtuins then have to reestablish that structure. They can put back 99.9% of those structures to how they were. But that .1% never goes back and accumulates over time. That is called ageing. </li></ol> To mitigate that, we need to upregulate the sirtuins through NAD boosters.

The role of sirtuins when it comes to ageing in the brain

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. Thank you to our sponsors:   Athletic Greens - https://athleticgreens.com/sinclair  Levels - https://levels.link/sinclair   InsideTracker - https://insidetracker.com/sinclair  Our Patreon page: https://www.patreon.com/davidsinclair  Lifespan book: https://amzn.to/3sUqurT Dr. David Sinclair Social:    Instagram   Twitter   Facebook  Matthew LaPlante's Social:    Twitter  To stay up to date with David's work to democratize biological age testing and insights, visit tallyhealth.com. Timestamps: (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 Flor (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 For the full show notes, including the peer-reviewed studies, visit the Lifespan podcast website. 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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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. Thank you to our sponsors:   Athletic Greens - https://athleticgreens.com/sinclair  Levels - https://levels.link/sinclair  InsideTracker - https://insidetracker.com/sinclair  Our Patreon page: https://www.patreon.com/davidsinclair  Lifespan book: https://amzn.to/3sUqurT Dr. David Sinclair Social:   Instagram   Twitter   Facebook  Matthew LaPlante's Social:    Twitter  To stay up to date with David's work to democratize biological age testing and insights, visit tallyhealth.com. Timestamps: (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 Flor (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 For the full show notes, including the peer-reviewed studies, visit the Lifespan podcast website. 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. Special thanks to our research assistants, Adiv Johnson & Sarah Ryan.

Join Dr. David Sinclair, Ph.D. in Lifespan, a popular health podcast that brings the cutting edge of aging and longevity science straight to you. Hear about the latest developments in aging research, lifestyle practices for longevity, exercise and nutrition science, and more.  This podcast 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.

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