Senior Scholar Award in Aging
Luca Cavalli-Sforza, M.D.
Stanford University School of Medicine

Genes Controlling Longevity in Centenarians

Subjects who can comfortably reach very old ages may have an advantageous consatellation of genes, giving them resistance to many causes of stress and disease, or may simply have one or more genes affecting the duration of their life. Such longevity genes have been observed in other organisms. The contribution to the study of aging we are planning aims at capitalizing on two distinct situations: one of them is the presence, in the P.I.'s laboratory at Stanford, of a new machinery developed for the purpose of detecting and testing DNA polymorphisms, i.e. differences in the DNAs of two individuals which can be as small as the replacement of a single nucleotide with another one, or its absence. The new method is called DHPLC (Denaturing High Performance Liquid Chromatopgraphy) and uses an addition to a classical HPLC apparatus, a column which can test fast and accurately the denaturation process of a DNA double helix. It was invented and patented by Drs. Peter Underhill and Peter Oefner in the P.I.'s laboratory. With this apparatus, genetic variants can be detected in genes potentially important also for the process of aging. The second situation is the collaboration with Prof. Giovanna De Benedictis of Cosenza, who has developed a project of study of Italian centenarians and has provided us with an adequate number of samples. The first gene we studied in centenarians was a gene whose mutants can cause premature aging: the Werner genes. A comparison of the genetic variation found in this gene among centenarians and among young subjects matched for geographic and ethnic origin, showed no variation. This approach is now being extended to a variety of other genes and chromosomal regions for which there is a probability that they may affect longevity.

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