2007•Cell MetabolismOpen access
Aging-Associated Reductions in AMP-Activated Protein Kinase Activity and Mitochondrial Biogenesis
Richard M. Reznick, Haihong Zong, Ji Li, Katsutaro Morino, Irene K. Moore, Hannah J. Yu, Zhen-Xiang Liu, Jianying Dong, Kirsty J. Mustard, Simon A. Hawley, Douglas E. Befroy, Marc Pypaert, D. Grahame Hardie, Lawrence H. Young, Gerald I. Shulman
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Abstract
Recent studies have demonstrated a strong relationship between aging-associated reductions in mitochondrial function, dysregulated intracellular lipid metabolism, and insulin resistance. Given the important role of the AMP-activated protein kinase (AMPK) in the regulation of fat oxidation and mitochondrial biogenesis, we examined AMPK activity in young and old rats and found that acute stimulation of AMPK-alpha(2) activity by 5'-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) and exercise was blunted in skeletal muscle of old rats. Furthermore, mitochondrial biogenesis in response to chronic activation of AMPK with beta-guanidinopropionic acid (beta-GPA) feeding was also diminished in old rats. These results suggest that aging-associated reductions in AMPK activity may be an important contributing factor in the reduced mitochondrial function and dysregulated intracellular lipid metabolism associated with aging.
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