Body: Lifespan by Dr. Savid Sinclair

Lifespan: why we age - and why we don’t have to
By Dr. Savid Sinclair
#1: Aging is a disease: We must move away from treating age-related diseases and focus on their root. Reclassifying aging as a disease is a critical first step in this shift in approach.
Sinclair believes we’re wasting money and time on what he calls “whack-a-mole” medic
“There is nothing more dangerous to us than age. Yet we have conceded its power over us. And we have turned our fight for better health in other directions.”ine.
Failure to define aging as a disease is also stunting research funding to understand the biology of aging. Billions of dollars go towards researchin cancer, heart disease and alzheimers.
Countries that move to this definition first will have a first-mover advantage.
#2: The Information Theory of Aging: The loss of analog information in the epigenome is the universal cause of aging.
Current consensus on aging: There is not one universal cause of aging. There are instead 8-9 hallmarks of aging, include telomere shortening, genomic instability, and mitochondrial dysfunction. Address one of them and you slow aging, address them all, and you could stop it.
Inclairs view: the information theory of aging: aging is caused by loss of information in our epigenome. Epigenome is what decides gene expression and alters development of cells. I see it as an instruction manual for different cells, when information is lost (like a scratched DVD), the resulting cells are less and less perfect.
#3: The longevity genes: Research is increasingly focusing on understanding the role of some specific longevity factors, such as sirtuins, NAD, and TOR. This would help stop/fix the loss of information described above.
#4: Activating the survival network: Research shows some day-to-day practices, such as calorie restriction, intermittent fasting and cold exposure, can activate our longevity genes and potentially extend lifespan.
The commonality of these longevity genes is that they are all activated in response to biological stress. Some activation may be key to delaying aging but overworking them leads to a loss of epigenetic information and aging.
Things we can do:
Eat less: Countless studies have shown significant increases in lifespans of mice and other mammals when calories are restricted over a large portion of their lives. Long-term calorie restriction may therefore increase lifespan, but it’s not an appealing solution.
Intermittent fasting: There is emerging evidence that we can cheat this process through periodic calorie restriction, regularly skipping a meal or fasting for a few days.
Lower protein, vegetable-rich diet: The reduction of amino acids (found in meats) leads to the inhibition of mTOR (which can help protect mitochondria from damage). Evidence on the reduced risk of heart disease, cancer and other diseases is now widely accepted.
Exercise: More frequent exercisers have larger telomeres in studies. Exercise appears to shift cells into survival mode, raising NAD levels which in turn activates the survival network, growing oxygen-carrying capillaries in muscles. High-intensity interval training appears to be the most effective form.
Cold exposure: Exposure to cold activate sirtuins, which in turn activates brown fat in our backs and shoulders. The presence of higher levels of this “brown fat” is associated with lower age-related disease.
Things that overwork our epigenome:
Smoking and passive smoking; pollution, PCBs and other chemicals in plastics; solvents and pesticides; food treated with sodium nitrate such as beer, cured meat, and cooked bacon; radiation from x-rays, gamma rays and UV light.
Sinclair recognises the impossibility of avoiding all these things, noting that the epigenome is set up to deal with a certain level of DNA breakages. The balance is ensuring we limit the damage as much as possible.
#5: Chemical and technological routes to longer life: Several existing drugs and future technologies offer the potential to extend lifespan and reduce age-related diseases.
Existing drugs and compounds:
Rapamycin: This lowers immune response and is used to facilitate organ transplant acceptance. Mice given small dosages in the final months of their lives lived 9%-14% longer.
Metformin: This is a diabetes drug which has also been linked to longer lifespan. In 25 out of 26 studies of rodents treated, metformin showed potential as a protector against cancer. It’s less toxic than rapamycin, but similarly mimics aspects of calorie restriction.
Resveratrol: This is a natural molecule found in red wine, grapes and berries – albeit in low quantities. Research has shown a positive impact on heart health, as well as 20% life extensions in mice.
NAD boosters: These are the emerging compounds of interest. Two variants (NR and NMN) both show promising signs, while research has also found that they may prolong fertility. No human trials have been conducted yet.
#6: Implications for our future: A longer-living global population poses a potential economic, political and environmental earthquake. Human innovation is capable of countering these dangers.
In the final pages, Sinclair reveals what he’s doing to extend his own life, declaring that he feels 30 at 50. Among other things, he takes a combination of metformin, NMN and resveratrol. Sinclair openly admits there are not human trials to support his drug concoction yet. We simply don’t know the long-term effect on human lifespan. Nevertheless, he is confident in taking his chances based on what he’s seen. (He may also be confident because he has an interest in their promotion, given the disclosures filed away at the end of the book.)
I won’t be taking his drug concoction just yet, because (1) it’s too expensive, (2) I’m not a mouse, and (3) I believe I’m young enough to wait for the outcome of human trials. That said, I will be taking some of the day-to-day practices into account, while keeping a close eye on how the science of aging progresses in the coming years and decades.
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Lifespan: why we age - and why we don’t have to
By Dr. Savid Sinclair
#1: Aging is a disease: We must move away from treating age-related diseases and focus on their root. Reclassifying aging as a disease is a critical first step in this shift in approach.
Sinclair believes we’re wasting money and time on what he calls “whack-a-mole” medic
“There is nothing more dangerous to us than age. Yet we have conceded its power over us. And we have turned our fight for better health in other directions.”ine.
Failure to define aging as a disease is also stunting research funding to understand the biology of aging. Billions of dollars go towards researchin cancer, heart disease and alzheimers.
Countries that move to this definition first will have a first-mover advantage.
#2: The Information Theory of Aging: The loss of analog information in the epigenome is the universal cause of aging.
Current consensus on aging: There is not one universal cause of aging. There are instead 8-9 hallmarks of aging, include telomere shortening, genomic instability, and mitochondrial dysfunction. Address one of them and you slow aging, address them all, and you could stop it.
Inclairs view: the information theory of aging: aging is caused by loss of information in our epigenome. Epigenome is what decides gene expression and alters development of cells. I see it as an instruction manual for different cells, when information is lost (like a scratched DVD), the resulting cells are less and less perfect.
#3: The longevity genes: Research is increasingly focusing on understanding the role of some specific longevity factors, such as sirtuins, NAD, and TOR. This would help stop/fix the loss of information described above.
#4: Activating the survival network: Research shows some day-to-day practices, such as calorie restriction, intermittent fasting and cold exposure, can activate our longevity genes and potentially extend lifespan.
The commonality of these longevity genes is that they are all activated in response to biological stress. Some activation may be key to delaying aging but overworking them leads to a loss of epigenetic information and aging.
Things we can do:
Eat less: Countless studies have shown significant increases in lifespans of mice and other mammals when calories are restricted over a large portion of their lives. Long-term calorie restriction may therefore increase lifespan, but it’s not an appealing solution.
Intermittent fasting: There is emerging evidence that we can cheat this process through periodic calorie restriction, regularly skipping a meal or fasting for a few days.
Lower protein, vegetable-rich diet: The reduction of amino acids (found in meats) leads to the inhibition of mTOR (which can help protect mitochondria from damage). Evidence on the reduced risk of heart disease, cancer and other diseases is now widely accepted.
Exercise: More frequent exercisers have larger telomeres in studies. Exercise appears to shift cells into survival mode, raising NAD levels which in turn activates the survival network, growing oxygen-carrying capillaries in muscles. High-intensity interval training appears to be the most effective form.
Cold exposure: Exposure to cold activate sirtuins, which in turn activates brown fat in our backs and shoulders. The presence of higher levels of this “brown fat” is associated with lower age-related disease.
Things that overwork our epigenome:
Smoking and passive smoking; pollution, PCBs and other chemicals in plastics; solvents and pesticides; food treated with sodium nitrate such as beer, cured meat, and cooked bacon; radiation from x-rays, gamma rays and UV light.
Sinclair recognises the impossibility of avoiding all these things, noting that the epigenome is set up to deal with a certain level of DNA breakages. The balance is ensuring we limit the damage as much as possible.
#5: Chemical and technological routes to longer life: Several existing drugs and future technologies offer the potential to extend lifespan and reduce age-related diseases.
Existing drugs and compounds:
Rapamycin: This lowers immune response and is used to facilitate organ transplant acceptance. Mice given small dosages in the final months of their lives lived 9%-14% longer.
Metformin: This is a diabetes drug which has also been linked to longer lifespan. In 25 out of 26 studies of rodents treated, metformin showed potential as a protector against cancer. It’s less toxic than rapamycin, but similarly mimics aspects of calorie restriction.
Resveratrol: This is a natural molecule found in red wine, grapes and berries – albeit in low quantities. Research has shown a positive impact on heart health, as well as 20% life extensions in mice.
NAD boosters: These are the emerging compounds of interest. Two variants (NR and NMN) both show promising signs, while research has also found that they may prolong fertility. No human trials have been conducted yet.
#6: Implications for our future: A longer-living global population poses a potential economic, political and environmental earthquake. Human innovation is capable of countering these dangers.
In the final pages, Sinclair reveals what he’s doing to extend his own life, declaring that he feels 30 at 50. Among other things, he takes a combination of metformin, NMN and resveratrol. Sinclair openly admits there are not human trials to support his drug concoction yet. We simply don’t know the long-term effect on human lifespan. Nevertheless, he is confident in taking his chances based on what he’s seen. (He may also be confident because he has an interest in their promotion, given the disclosures filed away at the end of the book.)
I won’t be taking his drug concoction just yet, because (1) it’s too expensive, (2) I’m not a mouse, and (3) I believe I’m young enough to wait for the outcome of human trials. That said, I will be taking some of the day-to-day practices into account, while keeping a close eye on how the science of aging progresses in the coming years and decades.
Subscribe!
If you enjoyed the podcast please subscribe and rate it. And of course, share with your friends!

See reason.fm/privacy-policy for privacy and opt-out information.

See reason.fm/privacy-policy for privacy and opt-out information.