Lifespan. David Sinclair
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David Gems would write that advances in our understanding of organismal senescence are all leading to a momentous singular conclusion: that aging is not an inevitable part of life but rather a “disease process with a broad spectrum of pathological consequences.”90 In this way of thinking, cancer, heart disease, Alzheimer’s, and other conditions we commonly associate with getting old are not necessarily diseases themselves but symptoms of something greater.
Or, put more simply and perhaps even more seditiously: aging itself is a disease.
THE LAW OF HUMAN MORTALITY
If the idea that aging is a disease sounds strange to you, you’re not alone. Physicians and researchers have been avoiding saying that for a long time. Aging, we’ve long been told, is simply the process of growing old. And growing old has long been seen as an inevitable part of life.
We see aging, after all, in nearly everything around us and, in particular, the things around us that look anything like us. The cows and pigs in our farms age. The dogs and cats in our homes do, too. The birds in the sky. The fish in the sea. The trees in the forest. The cells in our petri dishes. It always ends the same way: dust to dust.
The connection between death and aging is so strong that the inevitability of the former governed the way we came to define the latter. When European societies first began keeping public death certificates in the 1600s, aging was a respected cause of death. Descriptions such as “decrepitude” or “feebleness due to old age” were commonly accepted explanations for death. But according to the seventeenth-century English demographer John Graunt, who wrote Natural and Political Observations Mentioned in a Following Index, and Made upon the Bills of Mortality, so were “fright,” “grief,” and “vomiting.”
As we’ve moved forward in time, we’ve moved away from blaming death on old age. No one dies anymore from “getting old.” Over the past century, the Western medical community has come to believe not only that there is always a more immediate cause of death than aging but that it is imperative to identify that cause. In the past few decades, in fact, we’ve become rather fussy about this.
The World Health Organization’s International Classification of Diseases, a list of illnesses, symptoms, and external causes of injury, was launched in 1893 with 161 headings. Today there are more than 14,000, and in most places where records of death are kept, doctors and public health officials use these codes to record both immediate and underlying causes of disability and death.91 That, in turn, helps medical leaders and policy makers around the globe make public health decisions. Broadly speaking, the more often a cause shows up on a death certificate, the more attention society gives to fighting it. This is why heart disease, type 2 diabetes, and dementia are major focuses of research and interventionary medical care, while aging is not, even though aging is the greatest cause of all those diseases.
Age is sometimes considered an underlying factor at the end of someone’s life, but doctors never cite it as an immediate reason for death. Those who do run the risk of raising the ire of bureaucrats, who are prone to send the certificate back to the doctor for further information. Even worse, they are likely to endure the ridicule of their peers. David Gems, the deputy director of the Institute of Healthy Ageing at University College London and the same man who wrote the report from the Royal Society meeting on “the new science of aging,” told Medical Daily in 2015 that “the idea that people die of pure aging, without pathology, is nuts.”92
But this misses the point. Separating aging from disease obfuscates a truth about how we reach the ends of our lives: though it’s certainly important to know why someone fell from a cliff, it’s equally important to know what brought that person to the precipice in the first place.
Aging brings us to the precipice. Give any of us 100 years or so, and it brings us all there.
In 1825, the British actuary Benjamin Gompertz, a learned member of the Royal Society, tried to explain this upward limit with a “Law of Human Mortality,” essentially a mathematical description of aging. He wrote, “It is possible that death may be the consequence of two generally co-existing causes; the one, chance, without previous disposition to death or deterioration; the other, a deterioration, or an increased inability to withstand destruction.”93
The 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.94
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.95 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
“Decelerated aging,” Gems wrote, “has an element of tragic inevitability: its benefits to health compel us to pursue it, despite the transformation of human society, and even human nature, that this could entail.” D. Gems, “Tragedy and Delight: The Ethics of Decelerated Ageing,”
“You know the cartoon where Bugs Bunny is driving an old car that suddenly falls apart, every bolt sprung, with the last hubcap rattling in a circle until it comes to rest?”
“Really, people don’t die of old age,” Chris Weller wrote on Medical Daily. “Something else has to be going on.” C. Weller, “Can People Really Die of Old Age?,” “The Unexamined Life,” Medical Daily, January 21, 2015, http://www.medicaldaily.com/can-people-really-die-old-age-318528.
B. Gompertz, “On the Nature of the Function Expressive of the Law of Human Mortality, and on a New Mode of Determining the Value of Life Contingencies,”
D. A. Sinclair and L. Guarente, “Extrachromosomal rDNA Circles—A Cause of Aging in Yeast,”
Based on global population estimates and census reports, among other sources, the World Bank plotted out a fifty-six-year period ending in 2016 that showed life expectancy increasing from 52 to 72. “Life Expectancy at Birth, Total (Years),” The World Bank, https://data.worldbank.org/indicator/SP.DYN.LE00.IN.