Long-term exercise in mice has sex-dependent benefits on body composition and metabolism during aging

Abstract

Aging is associated with declining exercise and unhealthy changes in body composition. Exercise ameliorates certain adverse age-related physiological changes and protects against many chronic diseases. Despite these benefits, willingness to exercise and physiological responses to exercise vary widely, and long-term exercise and its benefits are difficult and costly to measure in humans. Furthermore, physiological effects of aging in humans are confounded with changes in lifestyle and environment. We used C57BL/6J mice to examine long-term patterns of exercise during aging and its physiological effects in a well-controlled environment. One-year-old male (n = 30) and female (n = 30) mice were divided into equal size cohorts and aged for an additional year. One cohort was given access to voluntary running wheels while another was denied exercise other than home cage movement. Body mass, composition, and metabolic traits were measured before, throughout, and after 1 year of treatment. Long-term exercise significantly prevented gains in body mass and body fat, while preventing loss of lean mass. We observed sex-dependent differences in body mass and composition trajectories during aging. Wheel running (distance, speed, duration) was greater in females than males and declined with age. We conclude that long-term exercise may serve as a preventive measure against age-related weight gain and body composition changes, and that mouse inbred strains can be used to characterize effects of long-term exercise and factors (e.g. sex, age) modulating these effects. These findings will facilitate studies on relationships between exercise and health in aging populations, including genetic predisposition and genotype-by-environment interactions.

Keywords: C57BL/6J; exercise training; mouse; physical activity; physiological response; voluntary running wheels.

Figure 1

Estimated marginal means and standard errors of (A) body mass (g), (B) percent body fat, and (C) percent lean mass beginning at approximately one year of age and extending over the course of the following year. Wheel access (experimental) or no wheel access (control) was granted after the measurement at ~1 year of age. (A) At all time points, General Linear Models (GLM) revealed that males weighed significantly more than females (P < 0.05) and, with the exception of age ~1 year (immediately prior to wheel access), wheel access significantly reduced mass (P < 0.05). No significant sex‐by‐wheel access interactions were detected. However, at ~1.1 years of age, following the first 51 days of wheel access, the sex‐by‐wheel access interaction (F _{1, 52} = 3.354; P = 0.073) suggested that wheel access reduced body mass to a greater extent among male mice. For panels (B) and (C), at a given mean age, an “i” indicates a significant (P < 0.05) interaction, a “s” indicates a significant effect of sex, and a “w” indicates a significant effect of wheel access on percent body fat.

Figure 2

Respiratory exchange ratio during aging and across experimental groups (sex; treatment). Repeated measure analysis of variance (ANOVAs) [GLM (SPSS, Chicago, IL)] revealed a significant effect of age across all groups (sex and experimental vs. control) (P < 0.05). Pairwise comparisons indicated that RER at ~ 2 years was significantly higher compared to ~1 year (P < 0.001) or ~1.5 years (P < 0.001). Additionally, within each treatment group a similar trend was observed ‐ asterisks represent results for within group pairwise comparisons.

Figure 3

Estimated marginal means and standard errors of mean (A) revolutions per day, (B) time (i.e., cumulative 1 min intervals in which at least 1 revolution was recorded) spent running, and (C) running speed (mean revolutions/mean running time) across 57 weeks. (A) Comparisons between sexes by General Linear Models (GLM) revealed females ran significantly more than males during weeks 1–45. During weeks 46–57 there was no significant difference between the sexes. (C) Comparisons between sexes by GLM revealed females ran significantly faster only during weeks 15, 16, 25, 26, 27, and 31.