The influence of age and captivity on cardiac structure and function in rhesus macaques.

Abstract

Captive non-human primates are widely used as models of aging, yet the conditions they live in differ markedly from their natural environment. Such environmental differences may influence how the cardiovascular system changes with age. This study characterized age-related cardiac phenotypes in free-ranging rhesus macaques and compared these patterns to captive-housed macaques to assess the influence of environment on cardiac structure and function across the lifespan. We performed transthoracic echocardiography in 133 free-ranging rhesus macaques (Macaca mulatta, aged 7-25 years, 41% female). Structural and functional cardiac parameters were compared between young (7-12 years; n = 48, 60% female) and old (18-26 years, n = 33, 42% female) free-ranging macaques. Then, controlling for age, we compared hallmark features of cardiac aging across and between free-ranging and captive-housed macaques (n = 317, 7-32 years, 73% female); where significant interactions were noted, slopes across age were compared. In free-ranging macaques, older individuals had greater interventricular septal thickness and relative wall thickness (RWT). Males exhibited larger left ventricular (LV) internal dimensions, wall thicknesses, LV mass, and LV volumes than females, but these differences were attenuated when indexed to body mass. Diastolic function was lower with advanced age, reflected by a lower E/A ratio, lower early diastolic tissue velocity (e') and greater atrial contraction velocity (a'). Compared with free-ranging macaques, captive animals exhibited lower age-adjusted diastolic function and had consistently thicker RWT. These findings provide the first characterization of age-related cardiac differences in free-ranging rhesus macaques, which parallel human aging, and emphasize the importance of ecological context when interpreting cardiac aging.