Aging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis

Cell Metab. 2007 Feb;5(2):151-6. doi: 10.1016/j.cmet.2007.01.008.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases
  • Aging*
  • Aminoimidazole Carboxamide / analogs & derivatives
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • Guanidines / administration & dosage
  • Guanidines / pharmacology
  • Male
  • Mitochondria / drug effects
  • Mitochondria / enzymology*
  • Multienzyme Complexes / metabolism*
  • Physical Conditioning, Animal
  • Propionates / administration & dosage
  • Propionates / pharmacology
  • Protein-Serine-Threonine Kinases / metabolism*
  • Rats
  • Rats, Inbred F344
  • Ribonucleotides / pharmacology

Substances

  • Guanidines
  • Multienzyme Complexes
  • Propionates
  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • Protein-Serine-Threonine Kinases
  • Stk11 protein, rat
  • AMP-Activated Protein Kinases
  • AICA ribonucleotide
  • guanidinopropionic acid