Lifespan: The Revolutionary Science of Why We Age—and Why We Don't Have To

by David A. Sinclair

There is no biological law that says we must age.

While it is interesting to speculate why our long lifespans first evolved—the need for grandparents to educate the tribe is one appealing theory—given the chaos that exists at the molecular scale, it’s a wonder we survive thirty seconds, let alone make it to our reproductive years, let alone reach 80 more often than not.

it is dead wrong. We do not die to make way for the next generation.

Kirkwood’s hypothesis explains why a mouse lives 3 years while some birds can live to 100.

These theories fit with observations and are generally accepted. Individuals don’t live forever because natural selection doesn’t select for immortality in a world where an existing body plan works perfectly well to pass along a body’s selfish genes.

But although we know with great certainty that radiation can cause all sorts of problems in our cells, it causes only a subset of the signs and symptoms we observe during aging,10 so it cannot serve as a universal theory.

Science has since demonstrated that the positive health effects attainable from an antioxidant-rich diet are more likely caused by stimulating the body’s natural defenses against aging, including boosting the production of the body’s enzymes that eliminate free radicals, not as a result of the antioxidant activity itself.

It’s a misconception that cloned animals age prematurely.

Today, analog information is more commonly referred to as the epigenome, meaning traits that are heritable that aren’t transmitted by genetic means.

In the same way that genetic information is stored as DNA, epigenetic information is stored in a structure called chromatin.

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.

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

our genes did not evolve to cause aging.

Youth → broken DNA → genome instability → disruption of DNA packaging and gene regulation (the epigenome) → loss of cell identity → cellular senescence → disease → death.

Remember, we’d done nothing to change the genome. We’d simply broken the mice’s DNA in places where there aren’t any genes and forced the cell to paste, or “ligate,” them back together. Just to make sure, later we broke the DNA in other places, too, with the same results. Those breaks had induced a sirtuin response. When those fixers went to work, their absence from their normal duties and presence on other parts of the genome altered the ways in which lots of genes were being expressed at the wrong time.

aging is not an inevitable part of life but rather a “disease process with a broad spectrum of pathological consequences.”

though smoking increases the risk of getting cancer fivefold, being 50 years old increases your cancer risk a hundredfold. By the age of 70, it is a thousandfold.21

being wrong has never stopped conventional wisdom from negatively impacting public policy.

And overwhelmingly that advice comes down to eating more vegetables, legumes, and whole grains, while consuming less meat, dairy products, and sugar.

After twenty-five years of researching aging and having read thousands of scientific papers, if there is one piece of advice I can offer, one surefire way to stay healthy longer, one thing you can do to maximize your lifespan right now, it’s this: eat less often.

There’s an adage in my field: if calorie restriction doesn’t make you live longer, it will certainly make you feel that way.

Red meat also contains carnitine, which gut bacteria convert to trimethylamine N-oxide, or TMAO, a chemical that is suspected of causing heart disease.

The levels of DNA-damaging aromatic amines in cigarette smoke are about fifty to sixty times as high in secondhand as in firsthand smoke.58 If you do smoke, it is worth trying to quit.

Textbooks and scientific papers depict biology as a static, two-dimensional world. Chemicals are drawn as sticks, biochemical pathways are arrows, DNA is a line, a gene is a rectangle, and enzymes are ovals, drawn thousands of times larger relative to the cell than they actually are.

Nobel Prize–winning physicist Richard Feynman expressed succinctly: “There is nothing in biology yet found that indicates the inevitability of death. This suggests to me that it is not at all inevitable and that it is only a matter of time before biologists discover what it is that is causing us the trouble.”

Science moves forward with small steps and big steps, but always one step at a time.

It seemed like a joke’s punch line—not only had we found a calorie-restriction mimetic, something that could extend longevity without hunger, but we’d found it in a bottle of red wine.

Ever wonder why organic foods, which are often grown under more stressful conditions, might be better for you?

For decades to come, NAD was simply a housekeeping chemical that teenage biology students had to learn about—with all the enthusiasm of a teenager doing housekeeping.

we evolved senescence as a rather clever trick to prevent cancer when we are in our 30s and 40s. Senescent cells, after all, don’t divide, which means that cells with mutations aren’t able to spread and form tumors. But if senescence evolved to prevent cancer, why would it eventually promote cancer in adjacent tissue, not to mention a host of other aging-related symptoms?

If smallpox were to return to our planet, after all, parents who refused to vaccinate their children would be pariahs of the lowest order. When safe and effective treatments are available for a common childhood disease, parents who refuse to save their children’s lives can have their guardianship overridden by the doctrine of parens patriae.

If He was going to maximize health benefits to offset the risks of the procedure, why not edit a gene that causes heart disease, which has an almost one-in-two chance of killing them?

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.

When we inoculate the herd, it doesn’t just protect us individually, it protects the weakest among us: the young and the old.

Governments don’t make vaccines; companies do.

“Embrace things rather than try and fight them. Work with things rather than try and run from them or prohibit them.”

knowledge is multiplicative and technologies are synergistic.

Consider, though, a world in which people in their 60s will be voting not for another twenty or thirty years but for another sixty or seventy.

As yet, there is really no evidence in modern times that population levels correlate with, let alone cause, increases in human misery.

Much to the contrary, in fact, our world is more populated today than it ever has been—and it’s a better place for more people, too.

for every dollar a government spends on education, that nation’s GDP grows on average by about $20.

Countries stagnate because they don’t innovate and don’t utilize their human capital, not because there aren’t enough jobs. This explains why countries with an earlier retirement age have a lower GDP.

In 1950, the US labor force participation rate of women was about 33 percent; by the turn of the century, it had nearly doubled. Tens of millions of women began working during those decades; that didn’t result in tens of millions of men losing their jobs.

No biological law says there is a limit to how long we can live; there is no scientific mandate that the average age at death must be 80 years.

the evidence that GMOs are safe is stronger than the evidence that climate change is occurring.