18 January 2004. What exactly distinguishes an old cell from a new one? Telomeres may be shorter, but for the most part, the genome hasn't changed. The cell’s collective protein supply, or proteome, is another matter, however. Anyone interested in studying aging cells may want to check out today's Nature Genetics. Hao Li, Cornelia Bargmann, Cynthia Kenyon, and colleagues at the University of California, San Francisco, report a transcriptome profiling method that identifies age-related patterns in gene expression across different species.
First author Steven McCarroll and colleagues first identified highly conserved orthologs (i.e., versions of the same, or corresponding gene) from different organisms, including flies and roundworms. They then used microarray analysis to compare transcriptional profiles of these orthologs in young and middle-aged animals. While the authors found that most age-related transcriptional changes occurred only in a given species, pair-wise comparisons between organisms revealed gene categories that are regulated by age.
The scientists found 14 such categories that were shared between Drosophila and C. elegans. These included proteins that were components of mitochondrial membranes, ion transporters, peptidases, and DNA repair proteins, to name just a few. Most proteins were downregulated as animals aged, but DNA repair proteins, peptidases, and proteins involved in catabolism were upregulated. The complete list of genes, which numbers in the hundreds, is available as a supplementary figure online.
The authors also used the profiling method to explore the timing of gene regulation. They found, for example, that both C. elegans and Drosophila turned on proteins involved in heat and oxidative stress responses at the same developmental stage—early adulthood—suggesting that these regulatory switches are developmentally timed, rather than being a response to accumulated damage.
One result that is of particular interest to those working on neurodegenerative diseases is that the authors found genes encoding transporter ATPases are repressed as animals age. This may offer a "candidate mechanistic connection between two features of aging: reduction in ATP synthesis and decline in the physiological activity of neurons, muscle, and excretory processes," the authors write.—Tom Fagan.
McCarroll SA, Murphy CT, Sou S, Pletcher SD, Chin C-S, Jan YN, Kenyon C, Bargmann CI, and Li H. Comparing genomic expression patterns across species identifies shared transcriptional profile in aging. Nat Genet. 2004 Jan 18 [Epub ahead of print].