Low resting metabolic rate is associated with greater lifespan because of a confounding effect of body fatness

A negative association between resting metabolic rate (RMR) and lifespan is the cornerstone of the rate of living and free-radical damage theories of aging. Empirical studies supporting a negative association of RMR to lifespan may arise from the correlation between RMR and both daily energy expenditure (DEE) and thermoregulatory activity energy expenditure (TAEE). We screened 540 female mice for higher and lower DEE and measured RMR in the resulting 324 (60 %). We then selected 92 mice in which there was no link between residual from the regression of RMR against body mass (BM) and residual of DEE against BM to separate the effects of these traits. Lifespan was not significantly related to body mass, DEE and TAEE, but significantly negatively related to RMR. Fat-free mass (FFM) and fat mass (FM) were both significantly positively related to RMR. After removing the effect of FFM on RMR, the association between RMR and lifespan remained significantly negative; however, after statistically removing the effect of FM on RMR, the significant association between RMR and lifespan disappeared. We conclude that the negative association between RMR and lifespan is primarily due to the effect of FM, with FM positively related to both RMR and mortality and hence RMR negatively to lifespan. In 40 additional screened mice, greater FM was also associated with greater oxidative damage to DNA. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11357-014-9731-3) contains supplementary material, which is available to authorized users.