Sci. Aging Knowl. Environ., 29 June 2005
Vol. 2005, Issue 26, p. nf50
[DOI: 10.1126/sageke.2005.26.nf50]


How Can We Craft a Better Theory to Explain the Evolution of Aging?

Science's 125th anniversary special issue

Mitch Leslie

The leading evolutionary explanation for senescence has hit middle age. Born in the late 1940s, the theory matured in the 1960s and flourished in the following decades, as researchers amassed evidence supporting its predictions. But like many of its contemporaries, the theory now needs to have a little work done. Evolution experts don't envision a makeover, merely a few nips and tucks to explain some vexing results from field studies and mathematical models.

How natural selection would permit organisms to deteriorate and die was an enigma until Peter Medawar's insights in 1946. The immunologist and Nobel laureate realized that because in nature many creatures perish from disease, predation, accidents, or other causes before they get old, natural selection's power declines with age (see "Aging Research Grows Up"). Because few organisms survive to their golden years (or weeks), detrimental genes can evade winnowing by natural selection if they act up late in life. Evolutionary biologist George C. Williams added another twist by arguing that some genes persist because they are pleiotropic: beneficial early in life but deleterious at older ages (see Williams Classic paper). In 1966, W. D. Hamilton wove these strands of thought into the first mathematical model demonstrating that selection weakens as organisms get older.

This intellectual framework proved its power in many studies. For instance, it predicts that creatures menaced by abundant predators should allot fewer resources to maintaining their bodies--and thus should age faster. One researcher found exactly that when he contrasted opossums living on an enemy-free island with those on the nearby mainland. Other work has confirmed that seemingly beneficial genes can also exact a price, as Williams predicted. Take the gene daf-2, part of the insulinlike growth factor pathway that governs worm metabolism and growth. Crippling the gene adds time in nematodes, but the loss saps their competitive prowess and ability to survive outside the petri dish (see "Death in the Dirt" and "Paying the Price").

But lately the theory has developed a few lines and blemishes. For example, research results on guppies clash with the opossum findings, indicating that fish swimming in waters teeming with hungry predators age more slowly than do their counterparts in safer habitats (see "Prey for Long Life"). Furthermore, a recent mathematical study argues that slightly modifying Hamilton's original equations can produce other evolutionary scenarios, including one in which natural selection strengthens with age. The work suggests that factors Hamilton didn't incorporate, such as how much of their limited energy organisms devote to reproduction, also affect how senescence evolves and need to be included in future models.

Rather than invalidating the theory, these discrepancies highlight the need to scrutinize the underlying assumptions and test them in actual populations. What we need to solidify current explanations, scientists say, is much more fieldwork on how different environments shape aging. To recognize broad patterns, researchers also need to look beyond the usual half-dozen lab animals. For example, studying species of fruit flies besides the experimental mainstay Drosophila melanogaster might help clarify how aging evolves in various habitats.

Such efforts might help resolve some controversial issues, such as evolutionary biologists' problem with sex. Specifically, they're unsure about how sex differences drive the evolution of aging. Female mammals usually outlive their mates, but in birds, males are often the longer-lived sex. A key question, researchers say, is how the sexes' mating "strategies" influence these life-span inequalities. To entice females, male animals often evolve flashy or costly ornaments--long tails, gaudy plumage, cumbersome antlers--that also hike their chances of being eaten or suffering injuries. For their part, female animals often fall for older mates. Because male showiness and female choices modify mortality and reproduction, both strategies might mold aging's evolution.

Another puzzle, according to some researchers, concerns what happens near the end of life. In humans and many other species, the mortality rate starts to rise in early adulthood and climbs exponentially until advanced ages, when it levels off. For instance, in adult humans the chances of dying double about every 8 years until about the age of 80. But a 95-year-old and a 103-year-old have about the same odds of perishing in any given year: about 50%. Why mortality stabilizes remains a mystery. It might reflect that only the hardiest individuals last to that age. But some models suggest that it might result from natural selection's power bottoming out late in life.

Researchers have identified some of the theory's problem areas, but they aren't ready to wheel it in for surgery. However, unlike plastic surgeons, who can promise only cosmetic changes to sagging jowls and drooping eyelids, they might be able to restore a middle-aged theory to its youthful vigor.

June 29, 2005 Citation: M. Leslie, How Can We Craft a Better Theory to Explain the Evolution of Aging? Sci. Aging Knowl. Environ. 2005 (26), nf50 (2005).

Science of Aging Knowledge Environment. ISSN 1539-6150