The renin–angiotensin system and prevention of age-related functional decline: where are we now?

Declining physical function is a major health problem for older adults as it is associated with multiple comorbidities and mortality. Exercise has been shown to improve physical function, though response to exercise is variable. Conversely, drugs targeting the renin–angiotensin system (RAS) pathway, including angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs), are also reported to improve physical function. In the past decade, significant strides have been made to understand the complexity and specificity of the RAS system as it pertains to physical function in older adults. Prior findings have also determined that interactions between antihypertensive medications and exercise may influence physical function above and beyond either factor alone. We review the latest research on RAS, exercise, and physical function for older adults. We also outline future research aims in this area, including genetic influences and clinical phenotyping, for the purpose of maintaining or improving physical function through tailored treatments.