Longevity, Quality, and the One-Hoss Shay

Science  03 Sep 2004:
Vol. 305, Issue 5689, pp. 1369
DOI: 10.1126/science.305.5689.1369

This special issue of Science is called “Piecing Together Human Aging” and its scientific content, as you will see in the following pages, is devoted mainly to the life and death cycles of the cells and tissues that compose our bodies. The topic ushers in some troubling thoughts about the way we wear out, as well as about the length of life and its quality—two features that are sometimes in conflict with one another. Let's start with the former: longevity. Demographers have always been interested in life expectancy, and in the problem of whether it has a finite, biologically conferred limit. The history of prediction in this area is a trail of busted estimates; proposed limits have been exceeded, one after another, since 1928, and there is no indication that a biological maximum of some kind is being closely approached. Most think such a maximum exists, but evidence from the steady improvement in life expectancy achieved by the best performers shows that it is still at a distance (Oeppen and Vaupel, Science, 10 May 2002, p. 1029).

Does that make us all feel better? Well, it depends—and that brings us to the quality-of-life issue, which has a lot to do with how we wear out. Oliver Wendell Holmes provided one metaphor for the perfect life-span in his poem “The Deacon's Masterpiece Or, the Wonderful One-Hoss Shay: A Logical Story.” The deacon completes this extraordinary project in 1755, the year of the great Lisbon earthquake. Built of carefully selected parts that the builder thought would wear out but not break down, it lasted exactly a hundred years in good condition. Then, on the centenary of the earthquake, the Wonderful One-Hoss Shay collapsed into a mound of dust, going to pieces “…all at once, and nothing first—just as bubbles do when they burst.” Its driver, the parson, was deposited unceremoniously onto the ground, right outside the meeting-house.

CREDIT: CORBIS

The shay's life cycle would be an attractive metaphor for us humans if the span were long enough. Alas, those of us at a Certain Age are all too acutely conscious of differential wear-out. As Roth et al. point out (p. 1423) in exploring the similarities between aging in humans and rhesus monkeys, there is a canonical sequence: presbyopia, cataracts, loss of motor activity, decline in memory performance. It would be nice if these things happened all at once instead of sequentially—as long as it wasn't too soon! How would you choose, for example, between the maximum human life-span (around 122 years) and a hundred years of perfect health followed by concurrent wear-out? My Aunt Margaret, like most of you, would choose the latter; she made it to 101, but said she didn't want many more years like the last few. (A sampler on the kitchen wall of her little house in Maine said: “It's hard to be nostalgic when you can't remember anything.”)

Alas, we will not be given the chance to trade quality for quantity in life's lottery. Biology is biology, and our different parts wear out on their own different trajectories. The task of aging-related research and geriatric medicine is to improve the quality of life during a period in which some loss of function is the order of the day. And the research reported in this issue, and in Science's two knowledge environments, SAGE (aging) and STKE (signal transduction), is beginning to suggest how cell and tissue death relate to organismal aging. How is replication failure related to cellular senescence? What is the role of telomere shortening and telomerase expression?

At the whole-organism level, we know that caloric restriction has a pronounced effect in promoting longevity. We still don't know how, although a variety of candidate mechanisms are now being proposed—including possible connections to the lowered insulin sensitivity in aging animals and people. Finally, we may well learn something from those genetic changes that produce effects that resemble aging, or progeria, explored in this issue by Kipling et al. (p. 1426). Research is unlikely to produce a future with the Holmesian hundred-year rectangular hyperbola, but just the same, we keep extending the human life-span. So we need to learn all we can about the cell biology of our weakest parts, while awaiting the appearance of some bionic deacon who can fix it so that they all last for a century.

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