ASHKENAZI

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. As published in the October 15, 2003 issue of the Journal of the American Medical Association, recent research findings showed that Ashkenazi centenarians and their children were three times more likely to have a DNA alteration in the CETP gene than the control groups. This mutation results in a single amino acid change in the CETP protein in affected individuals within the Ashkenazi population. Normal activity of the CETP gene is known to affect the levels and molecule size of the good (HDL) and bad (LDL) cholesterol. Lower levels of activity of the CETP gene appear to favorably change the lipoprotein profile. Subjects with this switch showed a decrease in plasma CETP levels, an increase in the amount of HDL cholesterol and an increase in the average size of the lipoproteins. This change may play a protective role in the development of cardiovascular disease, the leading cause of death in the US and the Western World. Higher levels of HDL are also associated with the prevention of deterioration of cognitive functioning. A statistically significant difference was noted in plasma HDL concentrations between subjects attaining higher (25-30) Mini Mental State Exam scores, and those scoring less than 25. Association of MMSE and HDL levels was of equal strength in men and women. Offspring of long-lived parents may inherit significantly better health. Offspring had significantly lower prevalence of hypertension (by 23%), diabetes mellitus (by 50%), heart attacks (by 60%) and strokes (no events reported), compared to several age-matched control groups. Grandparents of centenarians' offspring (born in ~1870) had a marked increase (~7 fold) in the "risk" for longevity, supporting the notion that genetics contributed to longevity in these famili