SEARCHING FOR LONGEVITY GENES IN HISTORICALLY UNIQUE JEWISH ASHKENAZI POPULATION

Our project's main hypothesis is that longevity is determined by specific genes that may function by slowing the aging processes and/or by protecting against common causes of death. We specifically chose individuals over the age of 95 because they are the most likely population to be enriched with longevity genes. The Ashkenazi Jews have a long history of isolation, inbreeding, and rapid expansion that resulted in the population being derived from a relatively limited number of founders. Thus, the genetic make-up of the founder population of the Ashkenazi Jews is unique and more homogeneous than most other populations. As a practical matter, this increases the likelihood of successfully identifying important genes using polymorphic genetic markers. In addition to obtaining data from the proband of the "oldest old" we similarly obtain data from their offspring. This is done for 2 major reasons, the first of which is genetic haplotyping. The second of which is because the offspring may be enriched with longevity genes, and we anticipate that in the future they may be followed prospectively. Furthermore, in addition to data from the general Ashkenazi population, we study the spouses of the offspring (if applicable) as an 'environment' matched control. We are in the process of near completion of gathering data from members of 20 units. We define a unit as a proband (n=20, 10013 years of age), as many offspring as possible (n=28), and the spouse of offspring (n=13). This data includes a questionnaire with relevant genetic/family history, health history, life style, and beliefs. Also we perform mini mental test, complete physical examination, and expiratory peak flow test. We obtained blood for DNA analysis and tests including SMA-20, lipid profile, complete blood count, and fibrinogen. Thus, we will continue to development of these instruments, and to establish a "bank" of DNA and phenotypical analysis, and determine the genetic and environmental factors, which enables certain people to elude death from the most common causes and to survive into a second century of life.