Effects of melatonin on nervous system aging: neurogenesis and neurodegeneration

J Pharmacol Sci. 2013 Sep 20;123(1):9-24. doi: 10.1254/jphs.13r01sr. Epub 2013 Aug 27.


Neural aging as a progressive loss of function involves central and peripheral post-mitotic neurons and neural stem cells (NSCs). It promotes neurodegeneration, impairs neurogenesis, and can be considered a cause of cognitive impairment and sensory and motor deficits in the elderly. Age-related morphological atrophic changes and cellular alterations are addressed by neural aging mechanisms. Neurogenesis declines during aging through several mechanisms such as an increase in quiescence state, changes in lineage fate, telomerase dysfunction, the failure of the DNA repair system, increased apoptosis, and the impairment of self-renewal. The self-renewal transcriptional factor Sox2 has been correlated with retrotransposon L1 and certain cell-cycle- and epigenetic-related factors, which are sometimes considered age-related factors in NSC aging. As neurogenesis decreases, non-mitotic neurons undergo neurodegeneration by oxidative stress, sirtuin, insulin signaling and mTOR alteration, mitochondrial dysfunction, and protein misfolding and aggregation. As neurodegeneration and impaired neurogenesis promote the nervous system aging process, the identification of neuronal anti-aging is required to raise life expectancy. The role of melatonin in increasing neurogenesis and protecting against neurodegeneration has been investigated. Here, we review nervous system aging that is correlated with mechanisms of neurodegeneration and the impairment of neurogenesis and evaluate the effects of melatonin on these processes.

Publication types

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

MeSH terms

  • Aged
  • Aging / drug effects*
  • Aging / genetics*
  • Aging / pathology
  • Aging / physiology
  • Animals
  • Apoptosis / genetics
  • Cognition Disorders / etiology
  • Humans
  • Melatonin / pharmacology*
  • Melatonin / physiology*
  • Nerve Degeneration / genetics
  • Nerve Degeneration / pathology
  • Nerve Degeneration / prevention & control*
  • Neural Stem Cells / pathology
  • Neural Stem Cells / physiology
  • Neurogenesis / drug effects*
  • Neurogenesis / genetics
  • Neurogenesis / physiology
  • Neurons / pathology
  • Neurons / physiology
  • Neuroprotective Agents*
  • Oxidative Stress / genetics
  • SOXB1 Transcription Factors / physiology


  • Neuroprotective Agents
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Melatonin