Antioxidant and antiaging activity of N-acetylserotonin and melatonin in the in vivo models

Ann N Y Acad Sci. 2001 Jun;939:190-9. doi: 10.1111/j.1749-6632.2001.tb03626.x.


It is generally accepted that antioxidant properties of melatonin significantly contribute to its antiaging effect. Antioxidant effects of N-acetylserotonin (NAS), a melatonin precursor and metabolite, might predict its antiaging action as well. The antiaging effect of NAS was studied in female retired breeders and male C3H mice. Both NAS and melatonin administered with drinking water prolonged life span in male animals by about 20% versus control animals (p < 0.01) but did not affect the life span of female mice. Antioxidative activity was evaluated by determining the malonaldehyde + 4-hydroxynonenal (MDA + 4-HNE) and cellular glutathion peroxidase (GPx) levels in male, 11-month-old, C57Bl/6J mice with very limited (if any) capacity to convert pineal NAS into melatonin. NAS increased the antioxidant capacity of kidney. Both NAS and melatonin (four weeks daily i.p. injections) increased the antioxidant capacity of brain as demonstrated by decreased MDA + 4-HNE and increased GPx levels. NAS-treated C57Bl/6J mice experienced a weight loss of 9%, whereas the saline and melatonin groups only 3%. NAS- and melatonin-treated animals had healthy and luxuriant fur coats with some gray fur in the melatonin group; animals in the saline group had large areas of baldness. This study demonstrates, for the first time, the antiaging effect of NAS. This effect needs to be confirmed in animals with impaired capacity to convert NAS into melatonin.

MeSH terms

  • Aging / drug effects*
  • Aging / metabolism
  • Aldehydes / metabolism
  • Animals
  • Antioxidants / pharmacology*
  • Body Weight / drug effects
  • Body Weight / physiology
  • Brain / drug effects*
  • Brain / metabolism
  • Female
  • Glutathione Peroxidase / drug effects
  • Glutathione Peroxidase / metabolism
  • Kidney / drug effects*
  • Kidney / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Melatonin / pharmacology*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Serotonin / analogs & derivatives
  • Serotonin / pharmacology*


  • Aldehydes
  • Antioxidants
  • Serotonin
  • Malondialdehyde
  • Glutathione Peroxidase
  • Melatonin
  • 4-hydroxy-2-nonenal
  • N-acetylserotonin