The Big Picture: New and improved microarray experiment reveals aging-related genomic changes (Genomics)
Authors: Davenport R. John 
Published: August 2003

Our foundations crumble over time, in part because cellular processes involved in a range of physiological activities--such as brain power, skin flexibility, muscle strength, and reproductive capacity--falter. Tracking the many gene activities necessary for those functions might elucidate the underpinnings of our decline. Scientists now report the most comprehensive genomewide analysis of aging to date. The study suggests that careful orchestration of gene activity doesn't generally fail with age. It also suggests how caloric restriction extends life-span: by slowing age-related changes in gene expression.

Recently, several teams have used microarrays to glean clues about aging (see
"Cornfields Fertilize Microarray Techniques"
). The results have been difficult to interpret: Within an experiment, similar test samples can give different readings; among experiments, the same design can give wildly different results. By repeating measurements many more times than others had done, Pletcher and colleagues have now advanced the robustness of such studies.

The researchers monitored changes in gene expression throughout the life-span of flies fed either full-strength or diluted food. They analyzed female flies at several ages, collecting three sets of animals from each group at every time point. The team prepared messenger RNA from each set, labeled it with a fluorescent tag, and applied the samples to DNA chips. Each chip contained probes for almost 13,000 genes; the fluorescence intensity at each spot indicates gene activity.

Expression of more than 1200 genes changed significantly as flies grew older. To determine which biological functions these genes affect, the team sorted them using the Gene Ontology database, which classifies genes based on their function and cellular location. The researchers pegged categories populated by a larger number of genes than would be expected by chance. In older flies, as predicted, they found that genes involved in reproduction tend to shut down, whereas those that respond to stress generally come to life.

The results further revealed that a reduced diet might impart longevity by retarding age-related changes in gene activity. Flies fed diluted food showed gene expression patterns similar to those of normally fed flies, but the patterns stretched out over their longer life-span. Additional analysis probed the notion that aging results from molecular damage that accumulates and breaks down an animal's ability to coordinate gene activity. If that were the case, older animals would display more chaotic patterns of gene expression than younger ones would. The team calculated the variability in gene expression among samples from flies of the same age. The range in expression levels did not expand with age, suggesting that aging does not result from global genetic anarchy.

One microarray experiment won't answer all questions about aging, says evolutionary biologist Michael Rose of the University of California, Irvine, but the study sets a new standard. Future investigations using similar approaches will help scientists flesh out the pathways involved in aging. Microarrays are "the right tool for the aging problem," says Rose. Scientists hope the tool will help them construct a solid understanding of the processes that reduce us to rubble.

--R. John Davenport; suggested by Nick Bishop

S. D. Pletcher, S. J. Macdonald, R. Marguerie, U. Certa, S. C. Stearns, D. B. Goldstein, L. Partridge, Genome-wide transcript profiles in aging and calorically restricted
Drosophila melanogaster. Curr. Biol.
12
, 712-723 (2002).
[Abstract]
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