Effects of Acarbose on Age-Related Declines in Motor and Cardiac Function

Age is a primary risk factor for chronic conditions including cardiovascular diseases.With inflation in the aged population over the last century, there is a growing need for interventions that directly target aging.Acarbose, an alpha-glucosidase inhibitor, is a promising aging intervention that increases lifespan in male and female mice by 22% and 5%, respectively (Harrison, 2013).Acarbose is an FDA approved anti-diabetic drug with a limited side effect profile.However, it has not been established if Acarbose has beneficial effects on healthspan(definition) or measures of functional health.We hypothesized that, in addition to lengthening lifespan, Acarbose would also diminish the effects of aging on motor and cardiac function.Using an outbred mouse model with young control, old control, and old Acarbose treated mice, motor function testing demonstrated a decline in functional health with age that was ameliorated by Acarbose treatment.Echocardiography showed concentric left ventricular hypertrophy with age in both males and females that was abrogated with Acarbose treatment in males.However, no significant declines in cardiac function were detected with age nor were any effects of Acarbose observed on cardiac function.Preliminary mass spectrometry analysis suggested that metabolism could play a role in the cardiac aging process, but no evidence suggested a role of Acarbose in reversing these agerelated changes.An ELISA based assay (PROCISE) also demonstrated a reduction in constitutive proteasome activity in the heart with age, but this was not affected by Acarbose.The findings that Acarbose ameliorates some functional declines seen with age and abrogates left ventricular hypertrophy in males furthers its promise as an aging intervention, but more research is needed into its effects in the heart and other physiological systems before it could serve as a clinically relevant drug for non-diabetic patients.