Mitochondrial decay in aging. Reversal through supplementation of acetyl-L-carnitine and N-tert-butyl-alpha-phenyl-nitrone

Ann N Y Acad Sci. 1998 Nov 20:854:214-23. doi: 10.1111/j.1749-6632.1998.tb09904.x.


We show that mitochondrial function in the majority of hepatocytes isolated from old rats (24 mo) is significantly impaired. Mitochondrial membrane potential, cardiolipin levels, respiratory control ratio, and overall cellular O2 consumption decline, and the level of oxidants increases. To examine whether dietary supplementation of micronutrients that may have become essential with age could reverse the decline in mitochondrial function, we supplemented the diet of old rats with 1% (w/v) acetyl-L-carnitine (ALCAR) in drinking water. ALCAR supplementation (1 month) resulted in significant increases in cellular respiration, mitochondrial membrane potential, and cardiolipin values. However, supplementation also increased the rate of oxidant production, indicating that the efficiency of mitochondrial electron transport had not improved. To counteract the potential increase in oxidative stress, animals were administered N-tert-butyl-alpha-phenyl-nitrone (30 mg/kg) (PBN) with or without ALCAR. Results showed that PBN significantly lowered oxidant production as measured by 2,7'-dichlorofluorescin diacetate (DCFH), even when ALCAR was coadministered to the animals. Thus, dietary supplementation with ALCAR, particularly in combination with PBN, improves mitochondrial function without a significant increase in oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcarnitine / administration & dosage
  • Acetylcarnitine / pharmacology*
  • Aging / metabolism*
  • Animals
  • Cells, Cultured
  • Cyclic N-Oxides
  • Dietary Supplements
  • Fluoresceins
  • Injections, Intraperitoneal
  • Liver / growth & development
  • Male
  • Mitochondria, Liver / drug effects
  • Mitochondria, Liver / metabolism*
  • Nitrogen Oxides / administration & dosage
  • Nitrogen Oxides / pharmacology*
  • Oxidants / metabolism
  • Oxygen Consumption / drug effects
  • Rats
  • Rats, Inbred F344


  • Cyclic N-Oxides
  • Fluoresceins
  • Nitrogen Oxides
  • Oxidants
  • diacetyldichlorofluorescein
  • phenyl-N-tert-butylnitrone
  • Acetylcarnitine