Many studies show that tweaking a single gene can extend life span in animal models. In a new study, Drs. Gil Atzmon and Nir Barzilai at the Albert Einstein College of Medicine of Yeshiva University have found that people harbor alleles--alternative forms of a gene--that confer the same sort of longevity advantage.
The researchers looked for genetic clues to longevity in a group of 214 Ashkenazi Jews who have passed or nearly reached 100 years of age. In the April 4 issue of PLoS Biology, they report that a specific genetic profile, or genotype, was associated with longevity as well as cardiovascular health, lower incidence of hypertension and healthy insulin metabolism.
"Since centenarians typically escape cardiovascular disease, diabetes, and other age-related disorders, we suspected these most senior of senior citizens might possess gene variations that help them reach a ripe old age," said Dr. Nir Barzilai, director of the Institute for Aging Research at Einstein and senior author on the paper. "If so, then these genotypes should occur with higher frequency in centenarians than in the rest of us."
Dr. Barzilai and his colleagues recruited Ashkenazi Jews for the study, because this population--descended from a founder group of just 30,000 or so people--is more genetically uniform than other groups, simplifying the challenge of associating a genotype with its physical manifestation (phenotype).
When studying centenarians, finding an age-matched control group is obviously difficult. But since longevity runs in families, the researchers were able to get around this problem by recruiting children of the centenarians and matching them against a control group consisting of other Ashkenazi Jews the same age.
Each participant had blood drawn--to determine their genotype and to measure levels of several cardiovascular disease markers including insulin, cholesterol, triglycerides, high-density lipoproteins (HDL, the "good" cholesterol), low-density lipoproteins (LDL, the "bad" cholesterol), and concentrations of two lipoprotein components called apolipoproteins (APO). In a previous study, the researchers had found that centenarians' LDL and HDL particle sizes are larger than normal, so these were also measured.
To identify genes associated with long life, they looked for single nucleotide polymorphisms (SNPs) in 36 genes involved in lipoprotein metabolism and other pathways linked to cardiovascular disease. (DNA contains four possible nucleotides--adenine, thymine, guanine and cytosine--and SNPs are variations of a single nucleotide in the DNA sequence.)