Resting metabolic rate declines with age, a situation that has evolved for perhaps much the same reasons as loss of stem cell function, in that it is one part of the trade-off between risk of death by cancer on the one hand versus organ failure due to faltering tissue maintenance on the other. Researchers here note that this reduction in resting metabolic rate is attenuated by the presence of age-related diseases. Why would age-related disease cause a relative increase in resting metabolic rate? Perhaps because the body is devoting more energy to fighting the condition, or perhaps the disease processes themselves, such as increased presence of senescent cells, result in greater metabolic activity.

Resting metabolic rate (RMR) changes over the life span and has been related to changes in health status. RMR reflects the energy expended by the human body in a prolonged resting state in the absence of food digestion, physical, or cognitive activities. As such, RMR can be understood as the “cost of living”, i.e., the energetic cost of maintaining all physiological processes that preserve homeostatic equilibrium and cognitive alertness and sets the stage for all activities of life. RMR is affected by changes in body size, with greater RMR associated with larger body size, especially large lean body mass. RMR is widely determined by the most metabolically active tissues, such as muscle, heart, brain, and liver, and, as the function and metabolic activity of these organs and tissues decline with aging, RMR also declines with aging.

In an analysis of data from the Baltimore Longitudinal Study of Aging (BLSA), subjects in good health and functional status had lower RMR than those affected by chronic diseases and functional limitations, independent of age, sex and body composition. Also, independent of relevant confounders, higher RMR was cross-sectionally associated with both a higher number of chronic diseases and with significantly higher risk of developing multimorbidity, defined as two or more out of 15 chronic conditions. Similarly, in community-dwelling women 60 years and older, increasing multimorbidity was associated with an increase in RMR independent of body composition and age. Moreover, two studies evaluating the longitudinal association between energy metabolism and mortality found higher RMR and 24 hour energy expenditure (24EE), which are predictive of future negative health outcomes and early mortality.

Overall, these data suggest that while healthy aging is associated with a progressive decline of RMR, independent of changes in body composition, superimposed adverse changes in health and functional status tend to attenuate such decline. This attenuation has been attributed to the potential extra-energetic cost of maintaining homeostasis in response to disease-related processes. However, a comprehensive analysis of how various diseases that ensue with aging affect age-associated changes in RMR is still lacking.

A hypothesis that could explain the increased basal metabolism observed in these conditions is the accumulation of senescent cells. The cell stops replicating, withdrawing from the cell cycle, and develops specific features such as resistance to apoptosis, increased energy metabolism, and production of bioactive molecules globally defined as “Senescence Associated Secretory Phenotype” (SASP). SASP includes several pro-inflammatory proteins that determine damage to tissues and produce a chronic inflammatory environment. We argue that the enhanced metabolic activity we observe in this analysis for some diseases could be attributable to the presence of increasing numbers of metabolically active senescent cells.