Aging elevates basal adenosine monophosphate-activated protein kinase (AMPK) activity and eliminates hypoxic activation of AMPK in mouse liver.

Despite the central role of adenosine monophosphate-activated protein kinase (AMPK) in the cellular stress response, it is unknown whether age-related changes in AMPK activity play a role in the diminished stress tolerance that is characteristic of aging. To address this question, we determined in the mouse liver how normal aging affects 1) basal AMPK activity, and 2) the degree to which AMPK activity is increased by in vivo hypoxia. We found that the basal activity of AMPK alpha1, but not alpha2, was higher in livers from 24-month-old mice compared to those from 5-month-old mice. Furthermore, while hypoxia elevated AMPK alpha1 and alpha2 activities in livers from 5-month-old mice, hypoxia failed to increase the activity of either isoform of AMPK in 24-month-old mice. These findings suggest that age-associated changes in hepatic AMPK activity may play a role in the physiological changes that occur in the liver with normal aging.