Genomewide Screens for Human Aging Genes

One of the primary goals of aging-related research is to identify genes that modify human aging and susceptibility to age-associated disease. Model systems have been particularly useful for providing candidate aging genes, by identifying mutations that significantly increase life span in lower eukaryotes. The relatively long life spans enjoyed by most people make analogous studies in humans impossible. Therefore, researchers are using several different indirect approaches to understand the genetic and environmental factors that affect aging in humans. High-throughput methods that employ new technologies for DNA sequence analysis are likely to prove particularly fruitful in this regard.

One approach toward identifying genes that modify human aging is to restrict the search space to individuals that demonstrate an extreme longevity trait, such as centenarians. Puca and colleagues have carried out a genome-wide linkage screen to identify loci that correlate with extreme longevity in centenarian sibships (Puca et al., 2001). From this screen, a locus on chromosome 4 was identified and was subsequently mapped to micro-somal transfer protein. Alleles of microsomal transfer protein have been associated with abetalipoproteinemia in humans (Geesaman et al., 2003), and it is likely that

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