AbstractThe biological clock exhibits circadian rhythms, with an endogenous period tau close to 24h. The circadian resonance theory proposes that lifespan is reduced when endogenous period goes far from 24h. It has been suggested that daily resetting of the circadian clock to the 24h external photoperiod might induce marginal costs that would accumulate over time and forward accelerate aging and affect fitness. In this study, we aimed to evaluate the link between the endogenous period and biomarkers of aging in order to investigate the mechanisms of the circadian resonance theory. We studied 39 middle-aged and aged Microcebus murinus, a nocturnal non-human primate whose endogenous period is about 23.1h, measuring the endogenous period of locomotor activity, as well as several physiological and behavioral parameters (rhythm fragmentation and amplitude, energetic expenditure, oxidative stress, insulin-like growth factor-1 (IGF-1) concentrations and cognitive performances) in both males and females. We found that aged males with tau far from 24h displayed increased oxidative stress. We also demonstrated a positive correlation between tau and IGF-1 concentrations, as well as learning performances, in males and females. Together these results suggest that a great deviation of tau from 24h leads to increased biomarkers of age-related impairments.Summary StatementThis manuscript describes how the misalignment between the endogenous circadian period and the 24h of the environmental periodicity impacts aging biomarkers and accelerates cognitive decline.