Longevity. Are we just a pill away from 150 years lifepans? =========================================================== https://medium.com/@sila_22801/longevity-are-we-just-a-pill-away-from-150-years-lifepans-bed4a8209498 Longevity. Are we just a pill away from 150 years lifepans? Longevity refers to the capacity to live for an extended period, exceeding the typical lifespan of a species. Diet, exercise, sleep, and stress management are of course important factors when it comes to longevity. But, in recent years it has been suggested that taking cerrtain compounds and supplements might have the potential to promote longevity. But well, is it true? Can we just take a pill, and then live to be a 150 years old? Sure, the body's ability to maintain homeostasis (a stable internal environment) changes with age. As people age, the ability to recover from illness or injury diminishes. But are there some ''switches'' inside the body that we can adjust, and then add years and years to our lifespans? According to Harvard researcher David Sinclair we are getting there. I.e. we will eventually get such a pill! And, needless to say, the internet is filled with suggestions for what such a pill could include. The master list. Not all that surprisingly the internet is also filled with people who are very sceptical: (David Sinclair) The longevity lie, David Sinclairs controversial claims, WSJ, ''Reverse Aging'' Guru David Sinclair and his trail of failed businesses. People want to believe that we are just one pill away from 150 year lifespans, and then they dont want to believe it... But lets investigate, what is it really that Sinclair says in the book ''Lifespan. Why we age''? Well, according to Sinclair (and others): Aging, and the diseases that follow, are probably the result of a number of factors. - Genomics instability caused by DNA damage. - Attrition of the protective chromosomal endcaps, the telemores. - Alterations to the epigenome that controls which genes are turned on and off - Loss of healthy protein maintenance, known as proteostasis. - Exhaustion of stem cells - Mitochondrial dysfunction. Etc. Without being a biologist, that sounds plausible, I imagine? I.e. "As every one of our cells has the same DNA, of course, so what differentiates a nerve cell from a skin cell is the epigenome... The collective term for the control systems and cellular structures that tell the cell which genes should be turned on, and which should remain off. And, this, far more than our genes, in is what actually controls much of our lives." P. 36. Stephen Helfand showed that adding extra copies of the dSir2 genes to fruitflies, suppresses epigenetic noise and extend their lifespan. Indeed, sirtuins prevent cellular senescence. It has a kind of an anti aging function. P. 43. If aging is caused by overworked epigenetic signalers responding to cellular insult and damage, it doesn't make much difference where the damage is. What matters is that there is damage and that sirtuins are rushing all over the place to address the damage, leaving their typical responsibilities and sometimes returning to other places. Along the genome. Where they are silencing things that aren't supposed to be silenced. P. 48. Certain genes are good to have. Eg. FOXO3 have been found in human communities in which people are known to enjoy both longer lifespans and healthspans. These FOXO3 variants likely turn on the bodies defenses against diseases and aging. Not just when times are tough, but throughout life P. 57. People taking Metformin has been shown to increase lifespan by nearly 6 percent. Mice taking Metformin showed reduces in cholesterol levels and improved physical performance. In 26 studies of of rodents treated er with metformin, 25 showed protection from cancer. Like rapamycin , metformin mimics aspects of calorie restriction. It activates AMPK , an it activates SIRT2. Increasing mitochondrial activity and removes misfolded proteins P. 125. mTOR, AMPK and sirtuins evolved to protect the body during times of adversity by activating survival mechanisms. When they are activated by low calorie or low-amino acid diets, organisms becomes healthier, disease resistant and longer lived. Molecules that tweak these pathways , such as rapamycin, metformin, resveratrol as nd NAD boosters can mimic the benefits of low calorie diets and exercise. P. 129. Again. Sounds plausible (at least if you do not know better, and is not a biologist…), so go ahead. Try to make some pills… Apparently, that was exactly what the company Sirtris Phramaceuticals did. Sold by Sinclair and co. to GlaxoSmithKline for $720 million. Harvard geneticist David Sinclair’s seductive notion that aging is a treatable disease has helped companies he founded to raise more than $1 billion. The investors have almost nothing to show for it. In the book Sinclair writes that a colleague told him: ''Just show that a molecule extend lifespan in mice, an the public will take it from there'' Well… Thats probably why science has to be a little bit more thorough than that. And not just about taking rapamycin, mesformin or NAD boosters — Without really being sure what it really does? Still, the idea of this magic pill is still out there. And who knows, someday it might become a reality? Sinclair wonders: ''What will the economy look like if people will begin to live, quite healthy into their 100s''. P. 230. And who will have access to life extending drugs. Everyone. Or just the rich? Will the rich and their pets end up living far longer than the poor? P. 233. In the end David Sinclair quotes ''Winnie the Pooh''. Indeed, that is always a nice way to end: What day is it today? Asked Pooh. It's today, squeaked Piglet. My favourite day, said Pooh. ---- Simon Laub. July 12th, 2025.