title: Aging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis.
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.
authors.affiliation: Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Reznick
authors.forename: Haihong
authors.initials: H
authors.lastname: Zong
authors.forename: Ji
authors.initials: J
authors.lastname: Li
authors.forename: Katsutaro
authors.initials: K
authors.lastname: Morino
authors.forename: Irene K
authors.initials: IK
authors.lastname: Moore
authors.forename: Hannah J
authors.initials: HJ
authors.lastname: Yu
authors.forename: Zhen-Xiang
authors.initials: ZX
authors.lastname: Liu
authors.forename: Jianying
authors.initials: J
authors.lastname: Dong
authors.forename: Kirsty J
authors.initials: KJ
authors.lastname: Mustard
authors.forename: Simon A
authors.initials: SA
authors.lastname: Hawley
authors.forename: Douglas
authors.initials: D
authors.lastname: Befroy
authors.forename: Marc
authors.initials: M
authors.lastname: Pypaert
authors.forename: D Grahame
authors.initials: DG
authors.lastname: Hardie
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Young
authors.forename: Gerald I
authors.initials: GI
authors.lastname: Shulman
mesh_terms: 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
chemical_list: 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