The impact of age and sex on body composition and glucose sensitivity in C57BL/6J mice

A paucity of data exists regarding sex differences in age‐related obesity and insulin resistance, particularly in the preclinical murine model. The purpose of this study was to determine the effects of age and sex on insulin action and body composition in C57BL/6J mice. Aged (AG, 18 months old) male C57BL/6J mice, glucose tolerance was diminished compared to young (YG, 6 months old) male mice (Area Under Curve: 95,103 ± 6818 vs. 64,005 ± 2031, P = 0.002). However, there was no age‐related decline in glucose or insulin tolerance in females. Body composition analysis revealed that AG males had significantly greater body mass (42.2 ± 1.9 vs. 30.0 ± 0.4 g, P < 0.0001), fat mass (18.7 ± 2.0 vs. 3.3 ± 0.4 g, P < 0.0001), body fat (43.0 ± 3.0 vs. 11.0 ± 1.5%, P < 0.0001) than YG males. In AG females, body mass (32.8 ± 1.6 vs. 26.3 ± 0.9 g, P = 0.02) was higher, but fat mass (13.3 ± 2.0 vs. 9.5 ± 1.3 g, P = 0.24) and body fat (37.8 ± 4.8 vs. 35.5 ± 3.8%, P = 0.67) were similar when compared to YG females. AG males had significantly higher body mass (42.2 ± 1.9 vs. 32.8 ± 1.6 g, P = 0.001) and fat mass (18.7 ± 2.0 vs. 13.3 ± 2.0 g, P = 0.04) compared to AG females; however, body fat (43.0 ± 3.0 vs. 37.8 ± 4.8%, P = 0.28) was similar. Six weeks of treatment with MitoQ, a mitochondrial‐targeted antioxidant, did not reverse age‐related obesity in male mice. Surprisingly, obesity and insulin resistance appear to be reversed in the oldest of the old male mice (28 vs. 20 months). Our findings indicate that female mice, unlike males, are protected from age‐related obesity and insulin resistance.