Being Mortal: Medicine and What Matters in the End

It turns out that inheritance has surprisingly little influence on longevity. James Vaupel, of the Max Planck Institute for Demographic Research, in Rostock, Germany, notes that only 3 percent of how long you’ll live, compared with the average, is explained by your parents’ longevity; by contrast, up to 90 percent of how tall you are is explained by your parents’ height. Even genetically identical twins vary widely in life span: the typical gap is more than fifteen years.

 

If our genes explain less than we imagined, the classical wear-and-tear model may explain more than we knew. Leonid Gavrilov, a researcher at the University of Chicago, argues that human beings fail the way all complex systems fail: randomly and gradually. As engineers have long recognized, simple devices typically do not age. They function reliably until a critical component fails, and the whole thing dies in an instant. A windup toy, for example, works smoothly until a gear rusts or a spring breaks, and then it doesn’t work at all. But complex systems—power plants, say—have to survive and function despite having thousands of critical, potentially fragile components. Engineers therefore design these machines with multiple layers of redundancy: with backup systems, and backup systems for the backup systems. The backups may not be as efficient as the first-line components, but they allow the machine to keep going even as damage accumulates. Gavrilov argues that, within the parameters established by our genes, that’s exactly how human beings appear to work. We have an extra kidney, an extra lung, an extra gonad, extra teeth. The DNA in our cells is frequently damaged under routine conditions, but our cells have a number of DNA repair systems. If a key gene is permanently damaged, there are usually extra copies of the gene nearby. And, if the entire cell dies, other cells can fill in.

 

Nonetheless, as the defects in a complex system increase, the time comes when just one more defect is enough to impair the whole, resulting in the condition known as frailty. It happens to power plants, cars, and large organizations. And it happens to us: eventually, one too many joints are damaged, one too many arteries calcify. There are no more backups. We wear down until we can’t wear down anymore.

 

It happens in a bewildering array of ways. Hair grows gray, for instance, simply because we run out of the pigment cells that give hair its color. The natural life cycle of the scalp’s pigment cells is just a few years. We rely on stem cells under the surface to migrate in and replace them. Gradually, however, the stem-cell reservoir is used up. By the age of fifty, as a result, half of the average person’s hairs have gone gray.

 

Inside skin cells, the mechanisms that clear out waste products slowly break down and the residue coalesces into a clot of gooey yellow-brown pigment known as lipofuscin. These are the age spots we see in skin. When lipofuscin accumulates in sweat glands, the sweat glands cannot function, which helps explain why we become so susceptible to heat stroke and heat exhaustion in old age.

 

The eyes go for different reasons. The lens is made of crystallin proteins that are tremendously durable, but they change chemically in ways that diminish their elasticity over time—hence the farsightedness that most people develop beginning in their fourth decade. The process also gradually yellows the lens. Even without cataracts (the whitish clouding of the lens that occurs with age, excessive ultraviolet exposure, high cholesterol, diabetes, and cigarette smoking), the amount of light reaching the retina of a healthy sixty-year-old is one-third that of a twenty-year-old.

 

I spoke to Felix Silverstone, who for twenty-four years was the senior geriatrician at the Parker Jewish Institute, in New York, and who has published more than a hundred studies on aging. There is, he told me, “no single, common cellular mechanism to the aging process.” Our bodies accumulate lipofuscin and oxygen free-radical damage and random DNA mutations and numerous other microcellular problems. The process is gradual and unrelenting.

 

I asked Silverstone whether gerontologists have discerned any particular, reproducible pathway to aging. “No,” he said. “We just fall apart.”

 

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