Higher Energy Expenditure in Humans Predicts Natural Mortality
Higher energy turnover is associated with shorter lifespan in animals, but evidence for this association in humans is limited. Over a century ago, the German physiologist Max Rubner linked body size and energy turnover with lifespan, and Benedict’s mouse-elephant curve extended these findings by demonstrating that smaller animals expend relatively more energy per body mass and have a shorter life span than larger animals. The physiological underpinnings of the theory that lifespan is determined by a rate of living, however, are not clear. The free radical theory of aging proposes that aging is accelerated by the accumulation of cellular metabolites, in particular toxic free radicals. Free radicals in the form of reactive oxygen species (ROS) accumulate more quickly with higher metabolic rates and are responsible for various types of oxidative damage in the cell. To investigate the hypothesis that higher metabolic rate is associated with aging, researchers examined whether energy expenditure (EE), measured in a metabolic chamber over 24 h and during rest predicts natural mortality in nondiabetic Pima Indians from the Gila River Indian Community.
In this longitudinal study, they found that 24EE and RMR, measured on different days, predict natural mortality in Pima Indians. These results are consistent with previously described data for RMR in an older population . In the present study, EE was measured in a younger population, and two different measures of EE provided consistent results.
Increased EE and ATP turnover increase free radical formation, and this is proposed as a mechanism for accelerated aging and increased mortality. Furthermore, studies in animals indicate that reduced metabolic rate after caloric restriction has beneficial effects on lifespan. However, recent studies using knockout models of key antioxidant genes in the worm Caenorhabditis elegans and data from long-lived mouse models have produced inconsistent results, therefore calling this oxidative damage theory into question.
Importantly, studies in which energy turnover is willfully increased (via physical activity) demonstrate clear metabolic benefits. Therefore, these results do not apply to increased energy turnover due to exercise. This belief is supported by two recent reports showing that 1) excess fat intake (which increases metabolic rates) leads to increased ROS production, which links overnutrition to insulin resistance, whereas 2) transient elevations in ROS induced by physical exercise may be essential for training induced insulin sensitivity. Thus, a transient elevation of ROS, as seen during physical exercise, could have beneficial effects on human health, whereas sustained elevations in ROS due to higher metabolic rates as a consequence of macronutrient excess could be harmful. Recent experiments have shown that transgenic hypermetabolic mice with increased uncoupling from ectopically expressed uncoupling protein 1 live longer than their wild-type counterparts. Despite higher metabolic rates, these mice show substantial reductions in mitochondrial ROS production. Together these data indicate that the effect of elevated metabolic rate on cell/organ damage over a lifespan needs to be viewed against the background of ROS production.
Jumpertz R, Hanson RL, Sievers ML, Bennett PH, Nelson RG, Krakoff J. Higher Energy Expenditure in Humans Predicts Natural Mortality. J Clin Endocrinol Metab:jc.2010-944. http://jcem.endojournals.org/cgi/content/abstract/jc.2010-2944v1 (Higher Energy Expenditure in Humans Predicts Natural Mortality -- Jumpertz et al., 10.1210/jc.2010-2944 -- Journal of Clinical Endocrinology & Metabolism)
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.
Higher energy turnover is associated with shorter lifespan in animals, but evidence for this association in humans is limited. Over a century ago, the German physiologist Max Rubner linked body size and energy turnover with lifespan, and Benedict’s mouse-elephant curve extended these findings by demonstrating that smaller animals expend relatively more energy per body mass and have a shorter life span than larger animals. The physiological underpinnings of the theory that lifespan is determined by a rate of living, however, are not clear. The free radical theory of aging proposes that aging is accelerated by the accumulation of cellular metabolites, in particular toxic free radicals. Free radicals in the form of reactive oxygen species (ROS) accumulate more quickly with higher metabolic rates and are responsible for various types of oxidative damage in the cell. To investigate the hypothesis that higher metabolic rate is associated with aging, researchers examined whether energy expenditure (EE), measured in a metabolic chamber over 24 h and during rest predicts natural mortality in nondiabetic Pima Indians from the Gila River Indian Community.
In this longitudinal study, they found that 24EE and RMR, measured on different days, predict natural mortality in Pima Indians. These results are consistent with previously described data for RMR in an older population . In the present study, EE was measured in a younger population, and two different measures of EE provided consistent results.
Increased EE and ATP turnover increase free radical formation, and this is proposed as a mechanism for accelerated aging and increased mortality. Furthermore, studies in animals indicate that reduced metabolic rate after caloric restriction has beneficial effects on lifespan. However, recent studies using knockout models of key antioxidant genes in the worm Caenorhabditis elegans and data from long-lived mouse models have produced inconsistent results, therefore calling this oxidative damage theory into question.
Importantly, studies in which energy turnover is willfully increased (via physical activity) demonstrate clear metabolic benefits. Therefore, these results do not apply to increased energy turnover due to exercise. This belief is supported by two recent reports showing that 1) excess fat intake (which increases metabolic rates) leads to increased ROS production, which links overnutrition to insulin resistance, whereas 2) transient elevations in ROS induced by physical exercise may be essential for training induced insulin sensitivity. Thus, a transient elevation of ROS, as seen during physical exercise, could have beneficial effects on human health, whereas sustained elevations in ROS due to higher metabolic rates as a consequence of macronutrient excess could be harmful. Recent experiments have shown that transgenic hypermetabolic mice with increased uncoupling from ectopically expressed uncoupling protein 1 live longer than their wild-type counterparts. Despite higher metabolic rates, these mice show substantial reductions in mitochondrial ROS production. Together these data indicate that the effect of elevated metabolic rate on cell/organ damage over a lifespan needs to be viewed against the background of ROS production.
Jumpertz R, Hanson RL, Sievers ML, Bennett PH, Nelson RG, Krakoff J. Higher Energy Expenditure in Humans Predicts Natural Mortality. J Clin Endocrinol Metab:jc.2010-944. http://jcem.endojournals.org/cgi/content/abstract/jc.2010-2944v1 (Higher Energy Expenditure in Humans Predicts Natural Mortality -- Jumpertz et al., 10.1210/jc.2010-2944 -- Journal of Clinical Endocrinology & Metabolism)
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.
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