Abstract P193: Metabolomic Profiles Associated With Longevity Women
Background: Identifying metabolite profiles associated with longevity may identify key pathways of healthy aging. The Framingham Heart Study previously identified 12 metabolites associated with longevity, but no studies have examined women specifically.
Methods: Of 2306 women in the Women’s Health Initiative (WHI) without known cardiovascular disease and with metabolomic profiles at baseline (1993-1998), 1386 were age 63 or older (potentially able to achieve age 85 years in 2015), and were not lost to follow-up before death or age 85. Liquid chromatography mass spectroscopy was used to measure metabolites, which were log-transformed and standardized. The 12 candidate metabolites were considered individually in logistic regression models to predict odds of attaining longevity (age ≥ 85): isocitrate, uridine, lysine, aconitate, histidine, malate, threonine, cotinine, C22:6 lysophophatidylcholine (LPC) and C38:6 phoshatidylcholine (PC). Models were initially adjusted for WHI arm and age (model 1), then additionally for baseline BMI, systolic blood pressure, hypertension, diabetes, smoking, total and HDL cholesterol (model 2). An FDR-adjusted p value <0.05 was defined as significant.Significant metabolites were all considered in a backward selection procedure (p for exclusion > 0.05). A composite score of these significant mutually-adjusted metabolites was created based on the quartile score for each metabolite, with higher values indicating higher likelihood of achieving longevity.
Results: The median baseline age was 71 years (range 63-79), and 712 women reached age ≥ 85. Ten of the 12 previously identified metabolites were significantly associated with longevity in this cohort in model 1; 8 remained significant in model 2 (FDR <0.05). When all 10 metabolites were considered together in a model and subjected to backwards selection, 3 remained significantly associated with longevity in model 2 (OR per SD [95% CI]): isocitrate (0.80 [0.70-0.91]) a substrate of the citric acid cycle, uridine (1.18 [1.04-1.34]) one of the five nucleosides making up nucleic acids, and lysine (1.24 [1.09-1.40]) an amino acid used in the biosynthesis of proteins. Women in the highest quartile of the 3 metabolite score had an OR of 2.24 (95% CI: 1.60-3.15) for longevity, compared to those in the lowest quartile of the score, after multivariate adjustment. Results for the score were significant for women both above and below the median age. For women <71 years, the highest score quartile was associated with an OR of 3.57 (2.22-5.76) for longevity, compared to the lowest.
Conclusions: Eight metabolites were found to be significantly associated with attaining longevity among women in the WHI. A score comprised of isocitrate, uridine and lysine was associated with a 2-3-fold higher odds of attaining longevity. Further research to understand the mechanisms between these metabolites and longevity is needed.
Author Disclosures: R. Balasubramanian: None. N. Paynter: None. F. Giulianini: None. J.E. Manson: None. J. Chen: None. M.Z. Vitolins: None. C. Clish: None. C.A. Albert: None. K.M. Rexrode: None.
- © 2017 by American Heart Association, Inc.