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Listening to Resveratrol

Could the famous ingredient of red wine herald a new era in medicine?

David Kent

Life's Natural Limits

In the July 1980 issue of the New England Journal of Medicine, James F. Fries proposed an influential model of health and illness based on the observation that there appear to be, even in the absence of disease, natural limits to the human lifespan. According to this view, aging is a natural and inevitable part of life. It is marked by a decline in organ function that begins in our 30s and eventually reaches a critical state in which even small perturbations in homeostasis cannot be tolerated. The benefits of modern medicine, it follows, would be confined to preventing premature death and compressing sickness toward the end of life, not fundamentally prolonging our natural lifespan.

Historical%20trends%20show%20an%20increasing%20Click to Enlarge ImageFries supported his model with a set of curves that plot survival against age over the 20th century (as shown in the graph). As the curves show, improvements in medicine and public health have increased average life expectancy at birth enormously (close to 30 years), whereas the life expectancy of an 80-year-old has hardly increased at all (about two years). This "rectangularization" of the life expectancy function lends support to Fries's concept of fundamental limits on the human lifespan, and suggests that—at least for richer segments of the population—life expectancy is approaching those limits. Therefore, according to Fries, in the future we should expect diminishing returns in mortality gains for new treatments of infectious diseases, cardiovascular diseases, cancer and the like. Medical innovation, he argued, should concentrate instead on living better, by "compressing" morbidity to the very end of life, not on living longer.

However, discoveries in more basic sciences, such as our developing understanding of sirtuin activators, suggest that this model may be at least half wrong. There may be natural limits to the mortality gains we should expect from disease-specific therapies, as Fries suggested. But by influencing the basic mechanisms underlying aging, medical innovations of the 21st century may yet increase the human lifespan in ways he did not foresee. Indeed, since the remaining frontier for mortality reduction is largely at the end of life, aging itself will have to be addressed and the shape of progress must be altered if there are to be any mortality gains from our huge investment in medical science and technology. Thus, a new set of curves, extending life expectancy beyond the frontier at the far right of the survival function, could well describe gains in life expectancy in the coming 100 years. 

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