Daily rhythms in metabolic and locomotor behaviour of prematurely ageing PolgA mice

Abstract

Ageing is an inherent and intricate biological process that takes place in living organisms as time progresses. It involves the decline of multiple physiological functions, leading to body structure and overall performance modifications. The ageing process differs among individuals and is influenced by various factors, including lifestyle, environment, and genetic makeup. Metabolic changes and reduced locomotor activity are common hallmarks of ageing. In the present study, we investigated the metabolic and activity phenotype in prematurely ageing PolgA(D257A/D257A) mice at 41-42 weeks by assessing parameters such as oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange ratio (RER), and locomotor activity using a metabolic cage for four days. Our findings revealed that VO2, VCO2, RER, locomotor activities, water intake, and feeding behaviour show a daily rhythm, aligning with roughly a 24-hour cycle. Female PolgA mice showed a significant reduction in locomotor activity compared to male PolgA and their age-matched wild-type littermates (WT), indicating an early sign of ageing. In addition, female PolgA mice displayed a distinct phenotype with reduced walking speed, body weight and grip strength in comparison to both male PolgA and WT mice. Taken together, our findings highlight the influence of sex on the manifestation of ageing traits in the PolgA mice and further suggest that PolgA mice could serve as a valuable model for investigating the intricate mechanisms underlying the ageing process.