Lifespan. Dr David A. Sinclair
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first part of the law says that there is an internal clock that ticks away at random, like the chance a glass at a restaurant will break; essentially a first-order rate reaction, similar to radioactive decay, with some glasses lasting far longer than most. The second part says that, as time passes, due to an unknown runaway process, humans experience an exponential increase in their probability of death. By adding these two components together, Gompertz could accurately predict deaths due to aging: the number of people alive after 50 drops precipitously, but there is a tail at the end where some “lucky” people remain alive beyond what you’d expect. His equations made his relatives, Sir Moses Montefiore and Nathan Mayer Rothschild, owners of the Alliance Insurance Company, a lot of money.
What Gompertz could not have known, but would have appreciated, is that most organisms obey his law: flies, roundworms, mice, even yeast cells. For larger organisms, we don’t know exactly what the two clocks are, but we do know in yeast cells: the chance clock is the formation of an rDNA circle, and the exponential clock is the replication and exponential increase in the numbers of rDNA circles, with the resulting movement of Sir2 away from the silent mating-type genes that causes sterility.8
Humans are more complicated, but in the nineteenth century, British mortality rates were becoming amenable to simple mathematical modeling because they were increasingly avoiding not-from-aging deaths: childbirth, accidents, and infections. This increasingly revealed the underlying and exponential incidence of death due to internal clocks as being the same as it ever was. During those times, the probability of dying doubled every eight years, an equation that left very little room for survivors after the age of 100.
That cap has generally held true ever since, even as the global average life expectancy jumped twenty years between 1960 and today.9 That’s because all that doubling adds up quickly. So even though most people who live in developed nations can now feel confident that they will make it to 80, these days the chances that any of us will reach a century is just 3 in 100. Getting to 115 is a 1-in-100-million proposition. And reaching 130 is a mathematical improbability of the highest order.
At least it is right now.
THE MORTAL BREEZE
Back in the mid-1990s, when I was pursuing my PhD at Australia’s University of New South Wales, my mother, Diana, was found to have a tumor the size of an orange in her left lung.
As she was a lifelong smoker, I’d suspected it was coming. It was the one thing we had argued about more than anything else. When I was a young boy, I used to steal her cigarettes and hide them. It infuriated her. The fact that she didn’t respond to my pleas to stop smoking infuriated me, too.
“I have lived a good life. The rest is a bonus,” she would say to me in her early 40s.
“Do you know how lucky you are to have been born? You’re throwing your life away! I won’t come visit you in hospital when you get cancer,” I would say.
When the cancer finally arrived about a decade later, I wasn’t angry. Tragedy has a way of vanquishing anger. I drove to the hospital, determined to solve any problem.
My mother was responsible for her own actions, but she was also a victim of an unscrupulous industry. Tobacco alone doesn’t kill people; it’s the combination of tobacco, genetics, and time that most often leads to death. She was diagnosed with cancer at the age of 50. That’s twenty-one years earlier than the first diagnosis in the average lung cancer patient. It’s also how old I am now.
In one way of thinking, my mother was unfortunate to develop cancer at such a young age. After her back was opened up, rows of ribs were cut from her spine, and major arteries were rerouted, she lived the rest of her life with just one lung, which certainly impacted her quality of life and ensured that she had only a few years of good life left.
On the genetics front, my mother was also unfortunate. Everyone in my family, from my grandmother to my youngest son, has had their genes analyzed by one of the companies that offer these services. When my mother had hers done, she learned, albeit after she had cancer, that she had inherited a mutation in the SERPINA1 gene, which is implicated in chronic obstructive pulmonary disease or emphysema. That meant her clock was ticking even faster. After her left lung was removed, her right lung was the sole provider of oxygen, but the deficiency in SERPINA1 meant that white blood cells attacked her remaining lung, destroying the tissue as if it were an invader. Eventually the lung gave out.10
In another way of thinking, though, my mother was very lucky—she had the come-to-God moment that many smokers need to go to battle with the tremendously powerful forces of addiction in time to save herself, and she spent another two decades on this planet. She traveled the world, visiting eighteen different countries. She met her grandchildren. She saw me give a TED Talk at the Sydney Opera House. For this we must certainly credit the doctors who removed her cancerous lung, but we should also acknowledge the positive impact of her age. One of the best ways to predict whether someone will survive a disease, after all, is to take a look at how old he or she is when diagnosed—and my mother was, relatively speaking, very young.
This is key. We know that smoking accelerates the aging clock and makes you more likely to die than a nonsmoker—15 years earlier, on average. So, we have fought it with public health campaigns, class action lawsuits, taxes on tobacco products, and legislation. We know that cancer makes you more likely to die, and we’ve fought it with billions of dollars’ worth of research aimed at ending it once and for all.
We know that aging makes you more likely to die, too, but we’ve accepted it as part of life.
It’s also worth noting that even before my mother was diagnosed with lung cancer—indeed, even before the cancerous cells in her lungs began growing out of control—she was aging. And in that way, of course, she was hardly unique. We know that the process of aging begins long before we notice it. And with the unfortunate exceptions of those whose lives are taken by the early onset of a hereditary ailment or a deadly pathogen, most people begin to experience at least some of the effects of aging long before they are impacted by the accumulation of diseases we commonly associate with growing old. At the molecular level, this starts to happen at a time in our lives that many of us still look and feel young. Girls who go through puberty earlier than normal, for example, have an accelerated epigenetic clock. At that age, we can’t hear the mistakes of the concert pianist.11 But they are there, even as a teenager.
In our 40s and 50s, we don’t often think about what it feels like to grow old. When I give talks about my research, sometimes I bring an “age suit” and ask a young volunteer to wear it. A neck brace reduces mobility in the neck, lead-lined jackets and wraps all over the body simulate weak muscles, earplugs reduce hearing, and ski goggles simulate cataracts. After a few minutes of walking around in the suit, the test subject is very relieved to take it off—and fortunately can do so.
“Imagine wearing it for a decade,” I say.
To put yourself into an aged mind-set, try this little experiment. Using your nondominant hand, write your name, address, and phone number while circling your opposite foot counterclockwise. That’s a rough approximation of what it feels like.
Different functions peak at different times for different people, but physical fitness, in general, begins to decline in our 20s and 30s. Men who run middle-distance races, for instance, are fastest around the age of 25, no matter how hard they train after that. The best female marathoners can stay competitive well into their late 20s and early 30s, but their times begin to rise quickly after 40. Occasionally, exceptionally fit outliers—such as National Football League quarterback Tom Brady, National Women’s Soccer League defender Christie Pearce, Major League Baseball outfielder Ichiro Suzuki, and tennis legend Martina Navratilova—demonstrate that professional athletes can stay competitive into their 40s, but almost no one remains at the highest levels of these or most other professional sports much past their mid-40s. Even someone as resilient as Navratilova peaked when she was in her early 20s through her early 30s.
There are some simple tests to determine how biologically old you probably are. The number of push-ups you can do is a good indicator. If you are over 45 and can do more than twenty,