Abnormal autonomic regulation of heart rate underlies age-related and sexdependent cardiac dysfunction in the small primate Microcebus murinus.

Ageing is a major risk factor for cardiovascular disease associated with the decline of maximal heart rate (HR) and HR variability (HRV). Such a decline could reduce cardiac adaptability to physiological needs and increase susceptibility to arrhythmias. The small primate Grey Mouse Lemur (Microcebus murinus), is a valuable model of ageing because it spontaneously develops neurodegenerative diseases. Moreover, in a lifetime it generates about three billion heartbeats as humans. Thus, it could also represent a new effective model to study cardiac ageing. We investigated cardiac responses to handling stress in young (1-5 years) and aged (6-12 years) lemurs of both sexes by using a mini-Holter for electrocardiogram (ECG) recordings. Moreover, we measured urinary catecholamine, the effect of pharmacological blockade of the autonomic modulation and cardiac contractility. Aged lemurs, particularly aged males, displayed slower HR and abnormal HRV under stress, delayed recovery of cardiac rhythm following stress and a dissociation between HR and HRV metrics. They also exhibited reduced adrenaline levels, a blunted response to pharmacological vagal blockade and diastolic dysfunction with preserved ejection fraction. These findings indicate that ageing, especially in male lemurs, impairs cardiac adaptation and recovery from stress through disrupted autonomic balance and sympathetic incompetence.