Mitochondrial decay in the brains of old rats: ameliorating effect of alpha-lipoic acid and acetyl-L-carnitine.
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.
Institute for Brain Aging and Dementia, University of California, Irvine, CA 92697-4540, USA.
Jiangang
J
Long
Feng
F
Gao
Liqi
L
Tong
Carl W
CW
Cotman
Bruce N
BN
Ames
Jiankang
J
Liu
D000108:Acetylcarnitine / Q000737:chemistry / Q000494:pharmacology*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress; D050050:Protein Carbonylation; D051381:Rats; D011916:Rats, Inbred F344; D013237:Stereoisomerism; D013482:Superoxide Dismutase / Q000378:metabolism; D008063:Thioctic Acid / Q000737:chemistry / Q000494:pharmacology*
D045222:Electron Transport Chain Complex Proteins; D008315:Malondialdehyde; D000108:Acetylcarnitine; D008063:Thioctic Acid; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione