College of LAS « Illinois

Ecology and Evolutionary Biology

Mutations of "Quiet" Genes Foster Aging

Theory on aging gets a boost from LAS research.

A theory that suggests the aging process might be safely slowed by targeting genes that are quiet early in life but may be damaging later on has gotten a boost from new findings from LAS.

The study provides the strongest support yet for the theory of mutation accumulation (MA), says Kimberly A. Hughes, an animal biologist in LAS. The theory, which has been difficult for scientists to test, proposes that aging is the result of an accumulation of mutations in genes that are active later in life. These genes are kept in check during reproductive years by selection processes that favor procreation. Examples are genes associated with Huntington's disease and forms of cancer that strike late in life.

The other, more widely accepted theory of antagonistic pleiotrophy (AP) says that aging occurs when genes that are helpful during the reproductive years such as those that produce estrogen take on harmful roles later in life. Under this theory, says Hughes, selection favors the genes' early-life effects because they lead to reproduction but it does not hinder the deleterious effects in late life.

The researchers' tests with fruit flies found that the deleterious effects of mutations on reproduction rose dramatically with age during the reproductive years in homozygous (those with many identical genes) and heterozygous (those with a variety of genes) lines. Reproductive success declined more rapidly, however, in the homozygous lines, as predicted by the MA theory. Although the study shows support for the MA theory, Huhes says the AP theory is not discounted. "These kinds of genes may be accumulating."

If geneticists try to remove bad late-in-life effects from a gene that has a positive role early in life, then its overall function could be harmed in future generations, Hughes says. Manipulating genes with no early-life benefits to negate their deleterious late-life effects may not cause negative evolutionary changes in the future.

Spring 2003