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MARGINALIA

The Undiscovered Country

The statistics of death show leaps in modern life expectancy but fail to answer the question: Why do we die?

Robert L. Dorit

Short-term Investments

A third class of evolutionary explanations for aging and death suggests that natural selection focuses largely on the young and the fertile and is indifferent to those past their reproductive years. In the years prior to reproduction, for instance, natural selection appears to suppress many genes that underlie disease. After reproduction, however, when such genes have comparatively minor effects on an organism's reproductive success (though not on its health), they are free to exert any malign influence. This scenario may explain why so many diseases, notably cancer and cardiovascular disease, increase precipitously in the fifth decade of our lives. Mutations that benefit the young—even if they cause problems later in life—will always gain traction.

Further support for an evolutionary approach to understanding death comes from the demonstration that fruit flies prevented from reproducing until late in life evolve significantly longer lifespans. By delaying reproduction, the experiment keeps natural selection in play for a longer amount of time, favoring genetic changes whose deleterious dark side is also delayed. In just a few generations, average lifespan increases. Nevertheless, harmful mutations eventually, inevitably accumulate into insurmountable, irreparable damage. These models lead to one conclusion: Aging and death occur when natural selection takes its eye off the ball in the later years.

A newer set of theories, prompted in part by our predilection for molecular explanation, have recently come on the scene. Such arguments—we'll call them fatalistic theories—suggest that a series of clocks tick away at the cellular level, marking our remaining time. They argue that evolution has programmed organisms to know when it is time to die. Critical to this argument is the observation that in a lab dish, most mammalian cells divide about 50 times and then die. We now know that chromosomes, those densely packed spools of DNA inside each cell, get shorter every time they're copied. Past a certain point, this chromosomal shortening kills the cell.

But we still can't connect the mechanisms of cell death with the mechanisms of our death (or, for that matter, the death of any other multicellular organism). Once again, the body is not just a collection of cells that behave independently. Our ability to repair and regenerate, to conscript circulating stem cells—whose chromosomes don't shorten when copied—into regenerating tissues and organs significantly complicates these hypotheses of aging and death.

More recently, some weight has been given to the idea that longevity is simply the result of certain trade-offs. Experiments showing that very low caloric intake (starvation) significantly increases lifespan suggest that there is a tradeoff between lifespan and active metabolism (which produces damaging chemical waste). Many studies in other species show a negative correlation between reproduction and longevity, suggesting that energy spent in reproduction would otherwise be spent in living a longer life. Some find in these trade-offs a guide for living. To me, their emphasis on the longevity benefits of an ascetic lifestyle sound slightly puritanical.

Ultimately, what does it suggest to have so many competing theories of death? I would argue it is the hallmark of a vibrant field, one in its early phases. The many explanations jostle and compete, driven by our shared belief that death may be inevitable, but it is not incomprehensible. The identification of genes involved in determining lifespan, the demonstration that lifestyle and environment can delay death, the technologies that extend life—all fuel our fascination with the topic. But the aging population in the developed world (including its scientists) also propels the field. In the end, however, if our real motivation is to loosen death's grip on humanity, we need to go beyond a material understanding of the biology of aging, lifespan and death. Most of humanity still does not die of old age, "sans teeth, sans eyes, sans taste, sans everything," as Jaques laments in As You Like It. Instead, most of humanity dies young, of preventable causes brought about by poverty and unequal access to health care. Any account of the causes of death that focuses solely on biology without considering the social and economic settings in which our biology plays out is at best incomplete, and at worse, misguided. Over my lifetime, cheating death may not be about tricking the limits of our biology, but instead about changing how we live our lives.

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