Kuakini Researchers Discover Human Gene Link to Longer Life
Kuakini Medical Center (KMC), the primary sponsor of the Hawaii Lifespan Study which is funded by the National Institute on Aging, and the study researchers subcontracted from Pacific Health Research Institute (PHRI) have identified a gene called FOXO3A that is linked with better health and a longer life. FOXO-related genes have been shown to prolong lifespan in other species but this is the first time that FOXO has been linked directly to longevity in humans. The findings from the Hawaii Lifespan Study were published in the September 1, 2008 issue of the Proceedings of the National Academy of Sciences.
Drs. Bradley Willcox, Tim Donlon, J. David Curb and colleagues at KMC and PHRI conducted a case-control study on the Kuakini Honolulu Heart Program/Kuakini Honolulu-Asia Aging Study cohort of 8,000 Japanese-American men who have had periodic health exams since the mid 1960s. The specimens used in the study are from biological samples and clinical data on the cohort that KMC has maintained since the start of the longitudinal studies. According to Dr. Willcox, no other study has tracked such a large group of men in such detail for this long amount of time.
“We screened 213 of the long-lived participants’ DNA and 402 of the average-lived, focusing on five genes in the insulin pathway,” said Willcox. “We then calculated how the DNA bases found at three locations on each gene were correlated with a comprehensive set of health criteria including chronic diseases, disability and insulin levels. What we found was very surprising and exciting.”
One location on the gene FOXO3A stood out. Of the four letters assigned to the chemical bases that make up DNA (A, T, C, G), the majority of study participants had the base thymine (T) on both chromosomes at this location. But those who had the base guanine (G) instead of T at this location had better health at the date of the original exam.
About 15 years later, the G was more highly represented in the subset of men who reached an average age of 98 years (range 95-106 years) compared with those who reached only an average age of 78 years. The effect was additive: those with one copy (carriers) of the G allele doubled their odds of living an average 98 years, with some living as long as 106 years. Men homozygous for the G allele (two G copies) almost tripled their odds of living nearly a century, faring even better than those who were heterozygous (one copy). Most importantly, GG men appeared markedly healthier at older ages.
Understanding human longevity is a complex endeavor with multiple determining factors. While non-genetic factors, including diet, physical activity, health habits, and psychosocial influences are important, up to 50% of the variation in human lifespan might be explained by genetic differences. Better understanding of the mechanisms of aging, including biological pathways that may have widespread influence on how we age, could have important implications for lowering our risk for age-related disease and disability. Such discoveries could help us live longer, healthier lives.