Genetics of aging

{BioPsy}} Genetics of aging is generally concerned with life extension associated with genetic alterations, rather than with accelerated aging diseases leading to reduction in lifespan.

The first mutation found to increase longevity in an animal was the age-1 gene in Caenorhabditis elegans. Michael Klass discovered that lifespan of C. elegans could be altered by mutations, but Klass believed that the effect was due to reduced food consumption (calorie restriction). Thomas Johnson later showed that life extension of up to 65% was due to the mutation itself rather than due to calorie restriction, and he named the gene age-1 in the expectation that other genes that control aging would be found. The age-1 gene encodes the catalytic subunit of class-I phosphatidylinositol 3-kinase (PI3K).

A decade after Johnson's discovery daf-2, one of the two genes that are essential for dauer larva formation, was shown by Cynthia Kenyon to double C. elegans lifespan. Kenyon showed that the daf-2 mutants, which would form dauers above 25 C would bypass the dauer state below 20 C with a doubling of lifespan. Prior to Kenyon's study it was commonly believed that lifespan could only be increased at the cost of a loss of reproductive capacity, but Kenyon's nematodes maintained youthful reproductive capacity as well as extended youth in general. Subsequent genetic modification (PI3K-null mutation) to C. elegans was shown to extend maximum life span tenfold.

According to the GenAge database of aging-related genes, there are over 800 genes extending lifespan in model organisms: 454 in the soil roundworm (Caenorhabditis elegans), 236 in the bakers' yeast (Saccharomyces cerevisiae), 79 in the fruit fly (Drosophila melanogaster) and 68 in the mouse (Mus musculus).

Genetic modifications in other species have not achieved as great a lifespan extension as have been seen for C. elegans. Drosophila melanogaster lifespan has been doubled. Genetic mutations in mice can increase maximum lifespan to 1.5 times normal, and up to 1.7 times normal when combined with calorie restriction.