Abstract 10472: Metabolomic Correlates of Longevity in the Community
BACKGROUND: Alterations in metabolism are hypothesized to influence lifespan as well as cardiovascular health, but data in humans are scant.
METHODS: We used liquid chromatography/mass spectrometry to determine plasma concentrations of 217 metabolites and examine their relation to longevity in participants of the Framingham Heart Study. First, we studied 647 individuals (mean age 67 years) who had the chance to attain age 80 during the 14-year follow-up period. Second, we studied cardiovascular and mortality endpoints among all 2,327 Framingham participants with metabolite profiling data available at baseline.
RESULTS: In multivariable analyses adjusting for traditional risk factors, higher levels of the citric acid cycle intermediate, isocitrate (OR 0.63 [95% CI 0.49-0.81], P=3.9x10-4), and the bile acid, taurocholate (OR 0.63 [0.48-0.83], P=7.4x10-4), were associated with lower odds of reaching age 80. In the larger sample, higher levels of isocitrate, but not taurocholate, were also associated with a lower American Heart Association ideal cardiovascular health score at baseline (Spearman’s rank correlation -0.29, P=6.6x10-13) and increased incidence of cardiovascular disease (adjusted HR 2.07 [1.31-3.26], P=0.002) and all-cause mortality (adjusted HR 2.32 [1.52-3.55], P=9.6x10-5). We replicated the mortality findings (adjusted HR 1.42 [1.02-1.98], P=0.04) in a sample from the Malmö Diet and Cancer study (N=325; mean age 58 years). No metabolites related to longevity were associated with the risk of developing cancer.
CONCLUSION: In our community-based investigation, biochemical profiling identified circulating metabolites not previously associated with longevity in humans. Our findings suggest that alterations in citric acid cycle activity are related to longevity at least partly through modulating cardiovascular risk. Further research is needed to investigate the potential underlying mechanisms.
- © 2013 by American Heart Association, Inc.