Sci. Aging Knowl. Environ., 19 May 2004
Oxidatively stressed and old flies turn on many similar genes
People complain that getting old is stressful, and now scientists might have proven them right. Many of the same genes change their output in old flies and oxidatively stressed young flies, suggesting that the aged insects are beleaguered on the molecular level. In addition, an aging-related increase in the activity of immune-system genes supports the notion that a general inflammatory response heightens as animals age. The results also reveal bursts of protein production that might eventually allow scientists to predict an individual fly's life span.
According to a prominent theory of aging, oxidative damage, caused by byproducts of metabolism, accumulates over time and makes the body crumble (see "The Two Faces of Oxygen"). Previously, scientists used microarrays to identify fly genes whose activities shift as the animals age (see "The Big Picture"). Molecular biologist John Tower of the University of Southern California in Los Angeles and colleagues wondered whether alterations in gene activity that are sparked by oxidative attack occur during aging.
To find out, the researchers removed messenger RNA from 61-day-old flies, 10-day-old flies, and 10-day-old flies subjected to a week in 100% oxygen, which speeds oxidative injury. They found that, among stressed flies and old flies, a total of 373 genes worked harder than they did in young, unstressed flies, and 882 genes slacked off. The identities of 97 of the activated genes and 154 of the quenched genes were the same in both the stressed flies and the old flies.
The researchers measured higher activity in genes known to crank up in stressed and old flies, but in both groups, they also saw increases in the activity of genes that help make purines--raw materials for DNA, antioxidants, and fuel. Tower's favorite explanation for this observation is that purine-based antioxidants combat aging-related stress. But he notes that oxidants scar purines, so the flies might be boosting production to replace molecules lost to stress or age-related damage. Although the activity of some immune-system genes surged in both groups of flies, about 10 genes ramped up only in old animals. These genes might provide a life-span predictor, allowing researchers to gauge a manipulation's effect on longevity before the flies die. To measure the protein output of the immune-system genes, the researchers hooked up three of them to a green-glowing marker. Quantities in young animals partly correlated with length of life span. Immune-system proteins might shield flies, Tower suggests, so insects with less protection die earlier.
The study shows that "old flies look stressed," says geneticist Scott Pletcher of Baylor College of Medicine in Houston, Texas. The result is significant, but he and Tower caution that the similarity in gene-activity alterations between the two groups of flies does not prove that stress causes aging, or vice versa. The rise in activity of immune-system genes supports the "emerging theme" that inflammation plays a role in aging, he adds. The work will prod scientists to find out whether a portion of that immune response arises from oxidative stress or from another trigger that turns on some of the same genes, Pletcher says. Teasing out connections between immunity, stress, and aging could eventually help take the angst out of growing old.
May 19, 2004
Science of Aging Knowledge Environment. ISSN 1539-6150