Hepatic mitochondrial dysfunction in senescence-accelerated mice: Correction by long-term, orally administered physiological levels of melatonin

Yuji Okatani, Akihiko Wakatsuki, Russel J. Reiter, Yasuyo Miyahara

Research output: Contribution to journalArticle

47 Scopus citations


Mitochondrial oxidative damage from free radicals may be a factor underlying aging. We investigated whether long-term administration of physiological levels of melatonin, a direct free radical scavenger and indirect antioxidant, influences mitochondrial respiratory activity in liver of senescence-accelerated mice (SAM). Liver was obtained in the middle of dark period of the daily light:dark cycle from SAMP8, a strain of mice prone to accelerated senescence, and from SAMR1, a senescence-resistant strain, at 6 and 12 months of age. Respiratory control index (RCI), adenosine-5 -diphosphate (ADP)/O ratio, State 3 respiration and dinitophenol (DNP)-dependent uncoupled respiration exhibited significant age-associated decreases in SAMP8. SAMP8 also showed significant age-associated reductions in respiratory chain complex I and IV activities. No age-related effects were found in these parameters in SAMR1. Daily oral melatonin administration (2 μg/mL of drinking fluid) beginning at 7 months of age significantly increased RCI, State 3 respiration, DNP-dependent uncoupled respiration, and complex I and IV activities in both mouse strains when they were 12 months old. These results reveal age-related reductions in mitochondrial function in SAM mice which are modified by melatonin; the most likely explanation for the corrective actions of melatonin relate to its antioxidative actions in mitochondria and other portions of the cell. The implication of the findings is that melatonin may be beneficial during aging as it reduces the deteriorative oxidative changes in mitochondria and other portions of the cell associated with advanced age.

Original languageEnglish (US)
Pages (from-to)127-133
Number of pages7
JournalJournal of pineal research
Issue number3
StatePublished - Oct 1 2002



  • Aging
  • Antioxidants
  • Free radical
  • Mitochondria
  • Respiratory chain
  • Senescence-accelerated mice

ASJC Scopus subject areas

  • Endocrinology

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