Importance of Primates for Pharmacology Research

The overwhelming majority of experiments in aging pathophysiology are conducted in rodent models. However, there are major species differences with humans, which can cause a major problem for drug development. One of the best examples from our laboratory was the development of beta 3 adrenergic receptors for cardiovascular function, obesity and diabetes. These drugs were effective in rodents and even some large mammalian models, but not in non‐human primates. The drugs failed in the clinics, with experience from humans, similar to the ineffectiveness in non‐human primates. Another major species difference is that rodents do not go through menopause and live for only 2–4 years. Accordingly, there are difficulties in extrapolating results in old females vs. old males to human pathophysiology. In contrast, aging female non‐human primates undergo menopause over several years, as do humans. We studied differences in left ventricular (LV) function in older primates, using the M.fascicularis model, which lives to an age in the late 20's to early 30's. There were 4 groups: young males (6.6±0.4 yrs); young females (5.5±0.5 yrs) and old males (25 ±0.3 yrs) and old females (24±0.5 yrs). As expected LV ejection fraction began to fall with aging in the males, i.e., it was significantly less, p<0.05, in old males (67±4.5%), than in young males (82±2.1%). In contrast, there were no significant differences in LV ejection fraction in old females, which were just entering menopause (73±8.3%), than in young females (79±4.6%). Thus, primates are potentially the best experimental animal model to evaluate new pharmacological therapies, particularly when related to aging and gender difference.