Differential effects of sex and age on daily and infradian rhythms of mice

Intrinsic biological rhythms regulate key physiological and behavioural processes, yet the influence of sex and age on these rhythms is not fully understood. We comprehensively examined 24 h (circadian) and >24 h (infradian; 5 and 10 day) rhythms in wheel-running and ingestive behaviours in single-housed young and middle-aged male and female mice. Circadian analysis revealed that middle-aged mice, particularly females, exhibited more precise daily rhythms and shifted a greater proportion of activity and feeding to the lights-on phase than young female mice. Middle-aged animals also ran for longer durations per day, suggesting age-related changes in activity regulation. Analysis of infradian rhythms further highlighted sex- and age-specific differences. Young female mice displayed robust 5 day rhythms in wheel-running activity, which were absent in middle-aged females. In contrast, few males (young or middle-aged) showed significant 5 day rhythms. Ten-day rhythms were most prominent in male mice, while females rarely expressed this periodicity. Physiologically, middle-aged mice lost more body weight in response to single housing, with middle-aged females being most affected. Interactions among behavioural rhythms in females also showed greater complexity, which increased with age. These findings reveal distinct sex- and age-dependent patterns in circadian and infradian rhythms as well as in physiological responses to isolation. Our work highlights the need to account for sex and age in chronobiological research, with broader implications for understanding vulnerability to age-related metabolic and behavioural disorders. KEY POINTS: Physiological findings: -Middle-aged mice lost more body weight after single housing, with females most affected. Circadian findings: -Older mice show more daytime activity. -Precision in daily rhythm differs by sex and age. -Middle-aged females showed prolonged daily wheel running. Infradian findings: -Young females had robust 5 day rhythms, absent in middle-aged females. -Some males showed 5 day rhythms, but 10 day rhythms were most prominent in males. Complexity of rhythms: -Complexity of interactions among behavioural rhythms increases with age, particularly in females.