The influence of ageing on the extrapineal melatonin synthetic pathway

Exp Gerontol. 2018 Sep:110:151-157. doi: 10.1016/j.exger.2018.06.010. Epub 2018 Jun 12.


Ageing affects various physiological and metabolic processes in a body and a progressive accumulation of oxidative damage stands out as often used explanation. One of the most powerful scavenger of reactive oxygen species (ROS) in all organs is melatonin. A majority of melatonin supplied to the body via blood originates from the pineal gland. However, we have been interested in a locally produced melatonin. We have used 2.5- and 36-months-old Wistar rats. Tissues were collected and gene expression of AA-NAT and ASMT, the two key enzymes in a synthesis of melatonin, was determined in brain, liver, kidney, heart, skin, and intestine. Since melatonin can influence antioxidant enzymes, the activity of superoxide dismutase (SOD) and catalase (CAT), and the level of GSH were measured in liver. In addition, Copper (Cu), Zinc (Zn), and Manganese (Mn) were also determined in liver since these microelements might affect the activity of antioxidant enzymes. The expression of AA-NAT and ASMT was increased in liver and skin of old animals. A positive correlation in AA-NAT and ASMT expression was observed in liver, intestine and kidney. Moreover, the activity of CAT enzyme in liver was increased while SOD activity was decreased. SOD and CAT were probably affected by the observed decreased amount of Cu, Zn, and Mn in liver of old animals. In our model, extrapineal melatonin pathway in ageing consisted of complex interplay of locally produced melatonin, activities of SOD and CAT, and adequate presence of Cu, Zn and Mn microelements in order to defend organs against oxidative damage.

Keywords: AA-NAT and ASMT; Catalase; Cu; Mn; SOD; Zn.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Animals
  • Antioxidants / metabolism
  • Catalase / metabolism
  • Copper / metabolism
  • Liver / metabolism*
  • Melatonin / metabolism*
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / metabolism
  • Zinc / metabolism


  • Antioxidants
  • Reactive Oxygen Species
  • Copper
  • Catalase
  • Superoxide Dismutase
  • Zinc
  • Melatonin