David A. Sinclair Quotes

Aging is controlled by single genes
Aging is slowed by adversity
Aging regulators can be modulated by small molecules
Aging is slowed by eating stressed plants
Aging is largely epigenetic noise
Cellular damage accelerates epigenetic age
Aging is a disease
Aging is reversible

Here's the important point: there are plenty of stressors that will activate longevity genes without damaging the cell, including certain types of exercise, intermittent fasting, low-protein diets, and exposure to hot and cold temperatures (I discuss this in chapter 4). That's called hormesis.28 Hormesis is generally good for organisms, especially when it can be induced without causing any lasting damage. When hormesis happens, all is well. And, in fact, all is better than well, because the little bit of stress that occurs when the genes are activated prompts the rest of the system to hunker down, to conserve, to survive a little longer. That's the start of longevity.

Here's the important point: there are plenty of stressors that will activate longevity genes without damaging the cell, including certain types of exercise, intermittent fasting, low-protein diets, and exposure to hot and cold temperatures (I discuss this in chapter 4).

Indeed, we know more about the health of our cars than we know about our own health. That's farcical. And it's about to change.

Don't be disheartened by my claim that we are the biological equivalent of an old DVD player. This is actually good news. If Szilard had turned out to be right about mutations causing aging, we would not be able to easily address it, because when information is lost without a backup, it is lost for good. Ask anyone who's tried to play or restore content from a DVD that's had an edge broken off: what is gone is gone. But we can usually recover information from a scratched DVD. And if I am right, the same kind of process is what it will take to reverse aging.

Like sirtuins, scientists have found TOR — called mTOR in mammals — in every organism in which they've looked for it. Like that of sirtuins, mTOR activity is exquisitely regulated by nutrients. And like the sirtuins, mTOR can signal cells in stress to hunker down and improve survival by boosting such activities as DNA repair, reducing inflammation caused by senescent cells, and, perhaps its most important function, digesting old proteins.27 When all is well and fine, TOR is a master driver of cell growth. It senses the amount of amino acids that is available and dictates how much protein is created in response. When it is inhibited, though, it forces cells to hunker down, dividing less and reusing old cellular components to maintain energy and extend survival — sort of like going to the junkyard to find parts with which to fix up an old car rather than buying a new one, a process called autophagy. When our ancestors were unsuccessful in bringing down a woolly mammoth and had to survive on meager rations of protein, it was the shutting down of mTOR that permitted them to survive.

Death by death, the world sheds ideas that need to be shed. Ipso facto, birth by birth, the world is offered an opportunity to do things better.

it. It is, in essence, a primordial survival kit that diverts energy to the area of greatest need, fixing what exists in times when the stresses of the world are conspiring to wreak havoc on the genome, while permitting reproduction only when more favorable times prevail.

simply keeping people alive — decades after their lives have become defined by pain, disease, frailty, and immobility — is no virtue.

The tragedy of the commons is that humans are not very good at taking personal action to solve collective problems. The trick to revolutionary change is finding ways to make self-interest align with the common good. For people to accept widespread biometric tracking in a way that could help us get ahead of fast-moving deadly viruses, they'll need to be offered something they have a hard time seeing themselves without.

The way doctors treat illness today "is simple," wrote S. Jay Olshansky, a demographer at the University of Illinois. "As soon as a disease appears, attack that disease as if nothing else is present; beat the disease down, and once you succeed, push the patient out the door until he or she faces the next challenge; then beat that one down. Repeat until failure."

The longevity genes I work on are called "sirtuins," named after the yeast SIR2 gene, the first one to be discovered. There are seven sirtuins in mammals, SIRT1 to SIRT7, and they are made by almost every cell in the body. When I started my research, sirtuins were barely on the scientific radar. Now this family of genes is at the forefront of medical research and drug development. Descended from gene B in M. superstes, sirtuins are enzymes that remove acetyl tags from histones and other proteins and, by doing so, change the packaging of the DNA, turning genes off and on when needed. These critical epigenetic regulators sit at the very top of cellular control systems, controlling our reproduction and our DNA repair. After a few billion years of advancement since the days of yeast, they have evolved to control our health, our fitness, and our very survival. They have also evolved to require a molecule called nicotinamide adenine dinucleotide, or NAD. As we will see later, the loss of NAD as we age, and the resulting decline in sirtuin activity, is thought to be a primary reason our bodies develop diseases when we are old but not when we are young.

Like rapamycin, metformin mimics aspects of calorie restriction. But instead of inhibiting TOR, it limits the metabolic reactions in mitochondria, slowing down the process by which our cellular powerhouses convert macronutrients into energy.20 The result is the activation of AMPK, an enzyme known for its ability to respond to low energy levels and restore the function of mitochondria. It also activates SIRT1, one of my lab's favorite proteins. Among other beneficial effects, metformin inhibits cancer cell metabolism, increases mitochondrial activity, and removes misfolded proteins.21

you were a member of the American upper middle class in the 1970s, you weren't just enjoying a more affluent life, you had a longer one, too. Those in the top half of the economy were living an average of 1.2 more years than those in the bottom half. By the early 2000s, the difference had increased dramatically. Those in the upper half of the income spectrum could expect nearly six additional years of life, and by 2018, the divide had widened, with the richest 10 percent of Americans living thirteen more years of life than the poorest 10 percent.40

What if we didn't have to worry that the clock was ticking? And what if I told you that soon — very soon, in fact — we won't?