Higher Energy Expenditure in Humans Predicts Natural Mortality

Context: Higher metabolic rates increase free radical formation, which may accelerate aging and lead to early mortality. Objective: Our objective was to determine whether higher metabolic rates measured by two different methods predict early natural mortality in humans. Design: Nondiabetic healthy Pima Indian volunteers (n = 652) were admitted to an inpatient unit for approximately 7 d as part of a longitudinal study of obesity and diabetes risk factors. Vital status of study participants was determined through December 31, 2006. Twenty-four-hour energy expenditure (24EE) was measured in 508 individuals, resting metabolic rate (RMR) was measured in 384 individuals, and 240 underwent both measurements on separate days. Data for 24EE were collected in a respiratory chamber between 1985 and 2006 with a mean (SD) follow-up time of 11.1 (6.5) yr and for RMR using an open-circuit respiratory hood system between 1982 and 2006 with a mean follow-up time of 15.4 (6.3) yr. Cox regression models were used to test the effect of EE on natural mortality, controlled for age, sex, and body weight. Results: In both groups, 27 natural deaths occurred during the study period. For each 100-kcal/24 h increase in EE, the risk of natural mortality increased by 1.29 (95% confidence interval = 1.00-1.66; P < 0.05) in the 24EE group and by 1.25 (95% confidence interval = 1.01-1.55; P < 0.05) in the RMR group, after adjustment for age, sex, and body weight in proportional hazard analyses. Conclusions: Higher metabolic rates as reflected by 24EE or RMR predict early natural mortality, indicating that higher energy turnover may accelerate aging in humans. (J Clin Endocrinol Metab 96: E972-E976, 2011)