A Molecular Map of Aging

A new genetic database could help reveal why animals age so differently.

Even closely related animals can have drastically different life spans, a fact that scientists have been puzzling over for years. Mice, which live about two years, got the short end of the longevity stick: their rodent cousin, the Southern flying squirrel, can live nearly 20 years. Chimps are 99 percent genetically identical to humans but live only half as long. Now a new resource could help pinpoint the genetic changes that underlie those differences.

Age map: Scientists compared age-related changes in gene expression in mice, humans, flies, and worms to try to pinpoint fundamental biochemical networks involved in aging; the results are shown here. Each row corresponds to a gene, while each column corresponds to a type of tissue. Genes that simultaneously decreased in different tissues of different animals are shown in blue, while those that increased are shown in yellow-green. The top row shows genes involved in energy production; these genes were the only set shown to decrease in every species studied. Credit: Zahn JM, Poosala S, Owen AB, Ingram DK, Lustig A, et al. (2007) AGEMAP: A Gene Expression Database for Aging in Mice. PLoS Genet 3(11)

In a study of mice, researchers at Stanford University and the National Institute on Aging (NIA) have generated a database that catalogues how gene expression--a measure of how active a gene is--changes in different parts of the body as the animals age. The researchers' findings suggest that different tissues age very differently, and this could help pinpoint when it is appropriate to use mice as a model of human aging--and when it's not.

Previous studies in both mice and humans have examined how gene expression changes with age in specific parts of the body, such as the brain or the kidneys. But the new study, commissioned by the NIA, analyzed simultaneously the activity of thousands of genes in 16 different tissues at different points during the animals' lives. That allowed researchers to compare age-related patterns of gene expression between different organs.

"One of the key lessons of this work is that to understand aging, we need to be thinking not in terms of individual genes, but of networks of genes and systems of different organs," says Daniel Promislow, a biologist at the University of Georgia in Athens, who was not involved in the project.

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The results, published this week in the journal PLoS Genetics, confirm the role of two processes believed to be major contributors to aging: slowed metabolism and increased inflammation. The expression of genes linked to both processes changed globally in aging mice. But the researchers also found large disparities in different tissues: expression profiles in the liver, brain, and muscle changed very little with age, while those in the lungs, the eyes, and the thymus (an immune organ) underwent the most radical transformation.

The researchers also found distinct patterns of aging in different tissues: neural, vascular, and endocrine tissue each had a characteristic expression profile. "It appears that the mouse has a mosaic of different things going on which may or may not be in synchrony with each other," says Stuart Kim, a biologist at Stanford who led the work. These patterns of gene-expression changes aren't clearly linked to oxidative stress--an excess of free radicals that damage cells--or other biochemical factors hypothesized to trigger aging, says Kim, so it's not yet clear how they influence aging.