Diminishing Effect of Exercise Training on AMPK Activity with Aging
Abstract Number: 1003-P
Authors: RICHARD M. REZNICK, GERALD I. SHULMAN.
Institutions: New Haven, CT.
Results: Recent nuclear magnetic resonance spectroscopy studies have suggested that age-associated reductions in skeletal muscle mitochondrial activity may be partially responsible for the accumulation of intramyocellular lipid in aging, causing insulin resistance. Given the key role of AMP-Activated Protein Kinase (AMPK) in the activation of lipid oxidation, inhibition of lipid synthesis, and induction of mitochondrial biogenesis, we hypothesized that age-associated reductions in exercise-induced AMPK activation may play a role in causing the increase in intramyocellular lipid content and reductions in mitochondrial function associated with aging. To test this hypothesis, YOUNG (3-month-old) and OLD (28-month-old) Fisher 344 rats underwent a progressive five-day exercise training program consisting of running on a treadmill at 85% MVO2Max for 30 min per day. Exercise training resulted in a 110% increase in AMPK-α2 subunit activity in the YOUNG group (P=0.04 compared to basal activity). In contrast, there was no increase in AMPK-α2 subunit activity in the OLD rats in response to exercise training. Furthermore, there was no increase in AMPK phosphorylation of serine 218 on acetyl-CoA carboxylase (ACC), a downstream target of AMPK, in the OLD rats following exercise training despite a 127% increase in the YOUNG rats (P=0.01 compared to basal). CONCLUSION: Activation of AMPK by exercise training is reduced in OLD rats. This age-associated reduction in exercise-induced AMPK activation may play an important role in causing reductions in mitochondrial function, increases in intramyocellular lipid, and insulin resistance in the elderly.