Mitochondrial Decay in the Brains of Old Rats: Ameliorating Effect of Alpha-Lipoic Acid and acetyl-L-carnitine

Neurochem Res. 2009 Apr;34(4):755-63. doi: 10.1007/s11064-008-9850-2. Epub 2008 Oct 10.


To investigate the mitochondrial decay and oxidative damage resulting from aging, the activities/kinetics of the mitochondrial complexes were examined in the brains of young and old rats as well as in old rats fed R-alpha-lipoic acid plus acetyl-L-carnitine (LA/ALC). The brain mitochondria of old rats, compared with young rats, had significantly decreased endogenous antioxidants and superoxide dismutase activity; more oxidative damage to lipids and proteins; and decreased activities of complex I, IV and V. Complex I showed a decrease in binding affinity (increase in K(m)) for substrates. Feeding LA/ALC to old rats partially restored age-associated mitochondrial dysfunction to the levels of the young rats. These results indicate that oxidative mitochondrial decay plays an important role in brain aging and that a combination of nutrients targeting mitochondria, such as LA/ALC, could ameliorate mitochondrial decay through preventing mitochondrial oxidative damage.

Publication types

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

MeSH terms

  • Acetylcarnitine / chemistry
  • Acetylcarnitine / pharmacology*
  • Aging / metabolism*
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Catalase / metabolism
  • Electron Transport Chain Complex Proteins / metabolism
  • Glutathione / metabolism
  • Lipid Peroxidation
  • Male
  • Malondialdehyde / metabolism
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Oxidative Stress
  • Protein Carbonylation
  • Rats
  • Rats, Inbred F344
  • Stereoisomerism
  • Superoxide Dismutase / metabolism
  • Thioctic Acid / chemistry
  • Thioctic Acid / pharmacology*


  • Electron Transport Chain Complex Proteins
  • Malondialdehyde
  • Acetylcarnitine
  • Thioctic Acid
  • Catalase
  • Superoxide Dismutase
  • Glutathione