Sci. Aging Knowl. Environ., 28 July 2004
New resource compiles genes that potentially influence human aging
R. John Davenporthttp://sageke.sciencemag.org/cgi/content/full/2004/30/nf69
A new online database can help researchers sort through a subset of longevity-associated genes. Launched 3 months ago and announced in print last week, GenAge offers a compendium of genes that are possibly linked to human aging. The new tool supplements SAGE KE's Genes/Interventions Database, which covers aging-related genes and life-stretching treatments in many organisms.
Keeping track of the swelling list of genes that apparently influence aging can tax even scientists who quote arcane papers from the 1950s at cocktail parties. Having this information in one place makes it easier to select genes to manipulate in experiments, figure out which genes collaborate, and hunt down papers that delve into a particular gene's function. Two Internet resources aid those endeavors. SAGE KE's Genes/Interventions Database compiles genetic manipulations and experimental treatments that tweak longevity in many creatures. GenAge, developed by gerontologists João Pedro de Magalhães of Harvard Medical School in Boston and Olivier Toussaint of the University of Namur in Belgium, now targets potential human aging-related genes.
Since SAGE KE's launch in 2001, the site's database has cataloged published genes and interventions--such as calorie restriction--that affect longevity in any organism. Each of the more than 200 entries for genes and 400 entries for interventions includes the organism involved, a description of the gene or treatment, a list of related genes in other organisms (for gene entries), pertinent references, and links to other databases such as WormBase and LocusLink. Visitors can search by organism, gene, key word, and other categories. Because few experiments have linked genes to mammalian aging, it contains 32 mammalian longevity genes, 10 of which are from humans.
De Magalhães and Toussaint took a different tack by focusing on human genes that might alter aging. First, they selected 20 genes that speed or slow mammalian decline, excluding some that might affect predisposition to disease rather than the aging process itself. Next, they picked other genes that work closely with those in the first set--for instance, those whose protein products operate in the same molecular pathway. Through "guilt by association," as de Magalhães describes the process, they devised a list of more than 200 human genes that might alter aging, although solid data don't exist for every one. GenAge excludes genes in model organisms such as worms or yeast. For instance, a search for daf-2--a nematode gene that dramatically extends worm life span when it malfunctions--yields no results. But the collection does contain a record for the insulin receptor, a mammalian counterpart to daf-2. Each entry includes a description of the rationale for inclusion, selected references, protein and DNA sequence information, and links to other databases such as Swiss-Prot and Ensembl. GenAge entries also supply a list of molecules that team up with the protein produced by each gene. For instance, the insulin receptor page specifies 11 molecules that grab the protein in cells, and one click reveals a diagram of those connections.
By casting a broad net for mammalian genes that potentially influence aging, GenAge "is really complementary to the SAGE KE database," says SAGE KE database curator Matthew Kaeberlein of the University of Washington, Seattle. GenAge's clearinghouse of protein networks "is very cool," says geneticist Valter Longo of the University of Southern California in Los Angeles, and it provides a quick reference for researchers who are unfamiliar with a protein's collaborators. This tool resembles the Connections Map on SAGE KE's sister site, the Signal Transduction Knowledge Environment, which details molecular circuits, although GenAge doesn't diagram entire pathways (for an example of a Connections Map pathway that might be involved in aging, see insulin signaling pathway).
A mammal-specific database will increase in importance as researchers gather new results, Longo says. But in the meantime, information on genes in nematodes, fruit flies, and yeast--such as that contained in SAGE KE's database--is crucial for the gerontology community, he says. Physiologist Simon Klebanov of Columbia University in New York City praises GenAge's slant toward mammals. Worms and yeast lend themselves to experimentation, but "you don't know what the result means for humans," he says. The new resource will undoubtedly help researchers keep tabs on the growing inventory of genes that contribute to an individual's demise.
July 28, 2004
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