A Means to an End: The Molecular Basis of Aging

Article excerpt

The phenomenon of aging is not a consequence of the evolutionary accumulation of "bad" genes but appears to be driven by molecular mechanisms that have been in place for billions of years.

The awareness that we are growing old may be uniquely human. Perhaps other animals, particularly higher mammals with rudimentary cognitive function, may be aware that they are slowing down with time, unable to keep up with others in their group, not as quick to find food, capture prey, or escape from danger. But we doubt they understand the full implications of the process. Humans, on the other hand, know only too well that the end point of aging is death. This knowledge drives in us a concern about the aging process--senescence--a concern that is lacking in other species.

Where did aging come from? Like other biological phenomena, aging may be assumed to have arisen through the processes of genetic variation and natural selection--mechanisms of evolution. When a new gene variant arises by modification of an existing gene, a decision has to be made to keep it or discard it. According to evolutionary theory, that decision is made on the basis of whether the variant raises the reproductive success of the corresponding organism. If it does, the variant gene will spread through the individual's offspring and, over time, to the rest of the species. If not, it will likely disappear in short order.

It is easy to see how this process of natural selection can work for traits like increased physical vigor, better eyesight, or brighter plumage for attracting mates. But how do we explain the inheritance of genes related to aging and death? As individuals get older, their ability to find mates, reproduce, and care for offspring is seriously impaired. How, then, could a trait so clearly contrary to the interests of the individual organism have been selected?

This issue is complicated by another factor: Most animals do not live long enough to experience serious aging. They die from disease or predation long before they become noticeably old. For most species, elderly individuals can be found only in zoos or laboratories, or as pets. In other words, the very trait that natural selection is supposed to act upon rarely shows up in nature. Yet, if kept in zoos or labs, animals do age. If the genes responsible for aging weren't picked up by natural selection, where did they come from?

One proposal is that aging may be triggered by genes such as the one responsible for Huntington's disease. We do not know what the normal Huntington's gene does, but inheritance of a single "bad" copy of this gene results in the development of a disorder that is uniformly lethal. This disorder, however, usually sets in only after the person is about 35--40 years of age--ample time for the patient to have passed on the gene to offspring. Some of the genes involved in Alzheimer's disease, and genes that predispose a person toward certain cancers, could also fall in this category. This proposal has become embedded in what is commonly called the "evolutionary theory of aging," which asserts that aging-related traits are the result of random accumulation of such genes over evolutionary time in different species.

Challenging a theory

Recent advances in molecular biology, however, suggest that this aspect of the evolutionary theory of aging is wrong. A study of the genes underlying aging and consequent "programmed" death in the simplest unicellular eukaryotes, such as paramecia and yeast, all the way through human beings, shows that these genes are remarkably similar in every species. Prof. Joan Valentine and her colleagues at the University of California, Los Angeles, have shown that genes involved in certain forms of cellular aging in humans continue to function when replacing equivalent aging genes in yeast, and vice versa.

This startling observation would not have been predictable from the evolutionary theory of aging. …