Aging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis.
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.
Reznick
Richard M
RM
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
Zong
Haihong
H
Li
Ji
J
Morino
Katsutaro
K
Moore
Irene K
IK
Yu
Hannah J
HJ
Liu
Zhen-Xiang
ZX
Dong
Jianying
J
Mustard
Kirsty J
KJ
Hawley
Simon A
SA
Befroy
Douglas
D
Pypaert
Marc
M
Hardie
D Grahame
DG
Young
Lawrence H
LH
Shulman
Gerald I
GI
D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; D000375:Aging; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D011422:Propionates / Q000008:administration & dosage / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012265:Ribonucleotides / Q000494:pharmacology
D006146:Guanidines; D009097:Multienzyme Complexes; D011422:Propionates; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D017346:Protein Serine-Threonine Kinases; C488755:Stk11 protein, rat; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; C005775:guanidinopropionic acid