Genes and Interventions That Influence Aging

These days, a significant proportion of research findings in the field relate to genes or environmental factors that adjust the rate of aging—usually in model organisms. A number of databases summarize key findings about such genes and interventions.

The U.S. National Library of Medicine's Online Mendelian Inheritance in Man (OMIM) catalogs human genes and disorders. Although it doesn't focus on aging-related conditions, it contains information about many diseases that disproportionately affect the elderly. For example, searching for ''Parkinson's Disease'' produces a list of several dozen genes. The summaries include information about the chromosomal location of the gene, activities of the protein it encodes and its purported or established role in disease, how the gene was cloned, a discussion of relevant animal models, and the history of its implication in disease. The write-ups are detailed and extensively referenced. NIH's Genetics Home Reference, too, supplies details about genes that have been associated with many aging-related disorders as well as other information on these illnesses. It includes entries for Alzheimer's disease, Parkinson's disease, and Hutch-inson-Gilford progeria syndrome, among many others.

For individuals who are interested in particular disorders with known or suspected genetic underpinnings, the Web serves up a number of focused resources. For example, Alzforum contains a database of genes and mutations that have been implicated in AD. The University of Washington's ''Werner Syndrome'' (WS) site hosts a repository for data on this premature aging disorder. The site's curators have compiled a list of mutations in the WRN gene that are associated with the condition, as well as diagnostic criteria, a historical overview of the topic, and a list of key papers. And the Diabetes Genome Anatomy Project homes in on the genetic underpinnings of this metabolic disease, whose risk increases with age.

Two databases focus specifically on genes that appear to alter the pace of aging: SAGE KE's Genes/Interventions Database and GenAge, directed by Pedro de Magalhaes at Harvard University. SAGE KE's database catalogues published genes and interventions—such as calorie restriction—that affect longevity or selected age-related diseases in any organism. Each of the more than 200 entries for genes and 400 entries for interventions includes the organism, 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. These write-ups function as crib sheets for the gene or intervention at hand and its association with aging. Visitors can search by organism, gene, key word, and other categories. Because few experiments have linked genes to mammalian aging, it contains only a few dozen mammalian longevity genes, a handful of which are from humans. GenAge takes a different tack, focusing on human genes that might influence the aging process. Its creators 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. This process yielded 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. 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.

The sites mentioned thus far center on any genes that influence aging or its maladies, but another spotlights genetic changes in a specific cell structure that has been connected with aging. According to some theories, glitches in mitochondrial DNA accumulated over years might cause organisms to break down by hampering energy production and increasing the generation of pernicious free radicals. MitoMap can aid in probing that idea. The site, curated by researchers at the University of California, Irvine, contains the sequence of the human mitochondrial genome, and organizes mitochondrial mutations into different categories, such as mutations that cause disease, inversions, and deletions. The site also features illustrations such as a mitochondrial genome diagram, a map of world migrations by humans based on data from mitochondrial DNA sequencing, and a model of how metabolic changes in the mitochondria might contribute to diabetes. MitoMap also lists links to other Web sites related to mitochondria.

For a different way to manage the literature, check out Telemakus. Produced by researchers at the University of Washington, the resource aims to organize publications in particular research areas and illuminate connections between related studies. The first database created by the project covers calorie restriction, a treatment that extends lifespan in many organisms. Users can browse the database by author, research findings, or organism, or can search for keywords. The description of each piece of work offers a summary of the study design, including the organisms studied, and the number, sex, and age of animals used. Entries also include a list of tables and figures from the publication and, in many cases, the figures and tables themselves, enabling visitors to quickly review a study's findings without leaving Telemakus or having to track down the original paper.

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