The biology of slowing and reversing aging with Dr. David Sinclair | Huberman Lab Podcast #52
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In a recent episode of the “Lifespan” podcast, Dr. David Sinclair explains his theory that aging is a disease that can be slowed or stopped through behavioral interventions, nutritional interventions, supplementation, and prescription drugs. Dr. Sinclair aims to provide listeners with information on the biology of aging and tools to intervene in the aging process through his new podcast. This episode of the Huberman Lab Podcast covers a range of anti-aging approaches, including some that have not been previously discussed in Dr. Sinclair’s book.
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According to Dr. David Sinclair’s research on aging discussed in a recent “Lifespan” podcast episode, aging is caused by “hallmarks,” including disruption of the epigenome, which controls gene activity. The epigenome is responsible for 80% of future health and longevity, and can be disrupted through factors such as methylation, leading to loss of cell function and identity. Adjusting the epigenome can potentially slow down or reverse aging, and its disruption can be measured to predict mortality.
Physical signs of aging include changes in DNA, postures such as a C-shaped spine, appearance of skin, and wrinkles. However, some centenarian families tend to look younger than their age, making their appearance a good indicator of aging. An AI system can also accurately predict someone’s age by looking at their face.
To control aging, people should be aware of the various factors that can accelerate it, such as broken chromosomes, DNA damage, and nerve pinching. It is possible to measure biological age, which can differ from chronological age, by tracking chemical levels. Development is an ongoing process throughout one’s life, with infancy and puberty being rapid stages of aging. Early developmental genes that get scratched can lead to aging. To slow or reverse aging, it’s crucial to take care of one’s body and environment by avoiding harmful chemicals, maintaining a healthy diet, and managing stress.
The rate of development during puberty can predict lifespan and health, with slower development leading to longer and healthier lives due to lower levels of growth hormone. Animals and people with low levels of growth hormone tend to live longer, and anecdotal evidence suggests that the actors who played the munchkins in the Wizard of Oz lived into their nineties or beyond. Overexertion or using growth hormone may feel good in the short term but can have negative long-term effects. Combining fasting and dwarf mutations with low growth hormone levels can potentially increase lifespan in mice and humans.
To slow down or reverse the effects of aging, it’s essential to take care of your body and environment by avoiding harmful chemicals, maintaining a healthy diet, and managing stress. Body size may have an impact on longevity, but the epigenome can change regardless of genes. Fasting can activate defensive genes and have a positive effect on lifespan, as well as not constantly eating and having low levels of insulin. Hunger could be an effective way to rest the body and re-establish the epigenome. When you eat during the day matters more than what you eat, and intermittent fasting can be achieved by skipping breakfast. However, it depends on each person’s hunger patterns if they also skip dinner. A healthy diet should avoid simple carbohydrates and sugar, mainly found in desserts, as they can cause plaque buildup and bad breath.
Fasting can have benefits for longevity and trigger the system of autophagy, which digests old and misfolded proteins in the body. Some people fast for up to 20 hours and eat within a four-hour window, while others fast for 16 hours and eat within an eight-hour window, and occasionally, some do longer fasts. Chaperone-mediated autophagy can kick in on day two or day three of a fast and get rid of deep proteins, potentially making an old mouse live 35% longer.
When fasting, it’s common to drink fluids and caffeine, and adding electrolytes can prevent lightheadedness and shakiness. Tea and coffee provide some beneficial substances, and supplementing electrolytes might be useful after a big night. The reasoning behind this is not clear.
To slow down the effects of aging, it’s recommended to keep blood sugar low for 24 hours or extend it for 2–3 days to trigger anti-aging mechanisms and remove dead cells. Glucose triggers longevity genes, which talk to each other and are affected by the body’s systems that detect food intake. Fasting activates sirtuin and down-regulates mTOR, leading to improved body defenses and energy. Sirtuin and mTOR pathways are the most important for longevity.
To slow down aging, it’s advised to avoid supplements like leucine that may trigger cellular growth, and instead, pulse periods of fasting to nourish the body. Supplementing with growth hormones or testosterone can have short-term benefits but may be damaging in the long run. A study revealed that mice given resveratrol every other day on a normal diet lived much longer than other mice. A longevity protocol involves pulsing, exercising, and taking supplements at the right time.
To slow down aging, it is recommended to take Metformin or a natural alternative like Berberine under the guidance of a doctor, as they can increase insulin sensitivity and reduce the risk of type two diabetes. However, caution is advised as high doses of Berberine may reduce lifespan. It is suggested to give your body a rest from supplements or meals every other day.
To effectively take resveratrol as a supplement to slow down aging, it is recommended to take a daily dose of 1000 milligrams of a light gray or white-colored supplement. Resveratrol needs to be taken with a fatty substance for absorption, which can be achieved by dissolving it in Greek yogurt or olive oil. Olive oil contains oleic acid, which activates sirtuin defenses, making it an ideal substance to take with resveratrol. A recommended method of taking resveratrol is by mixing it with olive oil, vinegar, and basil for a tasty and effective anti-aging protocol. Note that red wine is not a reliable source of resveratrol.
Fasting can slow down the effects of aging, but it depends on individual factors such as what was eaten the night before and whether the person has diabetes. There is no perfect solution for optimizing fasting, but it’s important to start gradually and not go cold turkey. The body doesn’t have a “breaking the fast switch” and only responds to glucose, AMPK, and mTOR. It’s crucial to balance rational and irrational approaches to fasting and supplementation, and to individualize your approach to fasting.
To slow down aging, it is advised to boost sirtuin activity through natural methods like exercise and fasting, as well as supplementation with resveratrol and NAD. NMN, a precursor to NAD, can double NAD levels in the blood and may have immediate effects on energy, vitality, and focus. Look for a reputable company that manufactures NMN under good manufacturing practices for optimal quality. Ongoing clinical trials will provide further insight into the benefits of NMN.
When it comes to artificial sweeteners, it’s best to be cautious and understand their potential impact on the gut microbiome. While Stevia is a naturally sourced product and has not been shown to be harmful, sugar-filled sodas should be avoided. Drinking a small amount of diet coke is not a major concern, equivalent to a “one” on a scale of 1 to 10. Sucralose is not equivalent to drinking a sugary soda. It’s important to keep in mind that the media can exaggerate stories and that science journalists should be required to post their credentials. This advice highlights the importance of moderation and critical thinking when consuming information.
Women should be aware of their increased iron needs due to menstruation, but excess iron can accelerate aging by increasing senescent cells. Therefore, excess iron supplements should be avoided, and personalized medicine is important to determine optimal health markers as the average human may not be the same as what’s optimal for an individual.
To optimize health and slow down aging, it’s recommended to track health data over time and use this information to inform personalized approaches to health, such as supplementation and exercise. While standard medical practice may focus on whether metrics are too high or low, more nuanced analysis is possible with data. Companies like InsideTracker offer affordable blood tests that people can take a couple of times a year to track their health, including blood sugar levels and inflammatory markers like CRP. It’s important to advocate for yourself and get a comprehensive blood test, even if you’re not sick, to stay informed about your health.
CRP is an early marker of macular degeneration, heart disease and other illnesses, and high levels of CRP can predict a future heart attack. It can be lowered by eating a healthier diet with more vegetables or taking anti-inflammatories. Statins are effective in reducing high cholesterol levels but may have long-term side effects. The advice given in the ’80s and ’90s about avoiding cholesterol is being challenged.
Consuming plant-based foods for high-density nutrition and xenohormetic molecules can possibly lead to slowing down aging and benefit human health. Animal-based amino acids should be avoided as they may have pro-aging effects. Antioxidants are not the key to longevity; instead, it’s important to understand mechanistic processes and turn on the body’s natural defenses against aging. Resveratrol’s ability to activate the body’s defenses, not its antioxidant properties, extends lifespan. Additionally, using behavioral tools to study aging and prolong lifespan is crucial.
Other ways to slow down aging include modulating DNA expression and function, improving the sirtuin pathway through methods like increasing NAD levels and sirt genes, maintaining muscle mass for healthy hormone levels, exploring the relationship between fasting and fertility in mice, using NMN to rejuvenate the female reproductive system in mice, investigating the potential for reactivating neuroplasticity through deprivation, and collaborating to explore the regulation of neuroplasticity.
According to recent research, the body has incredible powers of healing and recovery, including the ability to reset the aging process and rejuvenate cells in the skin, brain, and optic nerve. Human trials for a gene injection that reverses aging and restores vision are expected to begin soon. There is also hope for a single antibiotic injection to rejuvenate the entire body every five years. There are currently expensive tests available to detect medical problems, but more affordable options like at-home colon cancer tests are also available.
Challenge the body with cold exposure by using techniques like ice baths, cold water swims, and saunas. Following the Metabolic Winter Hypothesis and sleeping cool and dressing without many warm clothes can help thermoregulate the system and burn energy, potentially reducing the ongoing obesity epidemic. While some may not enjoy cold showers, alternatives like regular sauna use can be effective. If cold exposure is difficult, changes to diet and exercise can help compensate until it can be practiced regularly.
To slow down aging and optimize health, it’s important to avoid obesity as it can reduce NAD levels and accelerate aging. Fat contains senescent cells that secrete inflammatory molecules, and activating the sirtuin gene may extend lifespan. By inhibiting inflammation in the hypothalamus and controlling fertility through triggering GnRH, it may be possible to extend lifespan. Further research is needed to understand the mechanisms linking obesity and aging.
Recommendations to slow down aging and optimize health include avoiding harmful chemicals, maintaining a healthy diet, managing stress, tracking health data over time to inform personalized approaches, challenging the body through cold exposure and exercise, avoiding obesity, and understanding the detrimental effects of methylation and taking steps to address it. Using innovative tools and devices to monitor health conditions in real-time can be useful, rather than relying solely on yearly doctor visits.
When it comes to airport scanners and dental x-rays, Dr. David Sinclair advises people to be cautious due to the cumulative effects of radiation. He suggests opting for a pat-down at the airport or paying for TSA Pre to avoid scanners, and limiting the amount of dental x-rays one gets while acknowledging their usefulness for detecting cavities. Sinclair also believes that people should have a choice when it comes to exposing themselves to radiation.
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Link to podcast: https://www.youtube.com/watch?v=n9IxomBusuw&t=3366s
These notes are my take on the podcast and not word-for-word, so don’t come at me if they are not perfect. I did my best to get it right, but mistakes happen. So, take them with a grain of salt, use them as a map, and double-check the details by listening to the podcast yourself. Remember, if you take any action based on these notes, it’s all on you. Hope you find them helpful!
