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

Dawkins, T. G.; Curry, B. A.; Drane, A. L.; Rivas, V. N.; Ueda, Y.; Stern, J. A.; Phillips, D.; Negron-Del Valle, J.; Cayo Biobank Research Unit,; Higham, J. P.; Snyder-Mackler, N.; Brent, L.; Shave, R.

doi:10.1101/2025.10.20.683517

bioRxiv · 10.1101/2025.10.20.683517

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

Dawkins, T. G.·Curry, B. A.·Drane, A. L.·Rivas, V. N.·Ueda, Y.·Stern, J. A.·Phillips, D.·Negron-Del Valle, J.·Cayo Biobank Research Unit,·Higham, J. P.·Snyder-Mackler, N.·Brent, L.·Shave, R.

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Abstract

BackgroundCaptive non-human primates are widely used as models of human aging, yet the conditions they live in differ markedly from their naturalistic environment. Differences between captive and free-ranging environments may impact how the cardiovascular system adapts with age, potentially confounding studies of natural aging. This study characterized age-related cardiac phenotypes in free-ranging rhesus macaques and compared these patterns with their captive-housed counterparts to assess the influence of living environment on cardiac health across the lifespan. MethodologyWe performed transthoracic echocardiography in a cross-sectional cohort of 133 free-ranging rhesus macaques (Macaca mulatta, aged 7 - 25 years, 41 % female) living on Cayo Santiago, Puerto Rico. First, we compared structural and functional cardiac parameters between young (7 - 12 years; n = 48, 60% female) and old (18-26 years, n = 33, 42% female) free-ranging macaques. We then performed an ANCOVA, with age as a covariate, to compare cardiac structural and functional parameters between free-ranging and captive-housed macaques (n = 347, aged 7 - 32 years, 71% female). ResultsIn our free-ranging cohort, older macaques had greater interventricular septal thickness and relative wall thickness (RWT) than young. Males exhibited larger left ventricular (LV) internal dimensions, wall thickness, LV mass, and LV volumes than females, but these differences were attenuated when indexed to body mass. Diastolic function was lower with advanced age in both sexes, reflected by a lower E/A ratio, reduced myocardial tissue velocities during early diastole (e') and greater myocardial tissue velocities during atrial contraction (a). Compared with captive macaques, free-ranging animals exhibited better diastolic function, including a significantly higher E/A ratio, greater e, and lower a. Captive macaques also had significantly greater relative wall thickness across age and between sexes. Conclusions and implicationsOur study provides the first comprehensive characterization of age-related cardiac differences in free-ranging rhesus macaques, which show structural and functional cardiac differences similar to those observed with human aging. Captive macaques exhibited a more pronounced age-related cardiac phenotype than their free-ranging counterparts, including thicker left ventricular walls and lower diastolic function for a given age. These findings highlight the importance of considering the ecological context when interpreting animal models of cardiovascular aging.

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Dawkins, T. G., Curry, B. A., Drane, A. L., Rivas, V. N., Ueda, Y., Stern, J. A., Phillips, D., Negron-Del Valle, J., Cayo Biobank Research Unit,, Higham, J. P., Snyder-Mackler, N., Brent, L., Shave, R.. 2025-10-21. The influence of captivity on cardiac structure and function across age, in rhesus macaques. https://doi.org/10.1101/2025.10.20.683517

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