Immunosenescence-like state is accelerated by constant light exposure and counteracted by melatonin or turmeric administration through DJ-1/Nrf2 and P53/Bax pathways

J Photochem Photobiol B. 2018 Sep:186:69-80. doi: 10.1016/j.jphotobiol.2018.07.003. Epub 2018 Jul 9.

Abstract

The awareness of the interrelationship between immunosenescence and constant light exposure can provide new insights into the consequences of excessive exposure to light at night due to light pollution or shift work. Here, we investigated whether constant light exposure (LL) acts as an inducer of immunosenescence. We also determined the role of melatonin or turmeric in reversing the putative effects of constant light and explored for the first time the underlying molecular mechanisms. Young (3-4-month-old) rats were exposed daily to LL alone or in combination with each of melatonin and turmeric for 12 weeks. A group of aged rats (18-months old; n = 6) was used as a reference for natural immunosenescence. Constant light exposure resulted in remarkable pathophysiological alterations resembling those noticed in normal aged rats, manifested as apparent decreases in antioxidant activities as well as Nrf2 and DJ-1 expressions, striking augmentation in oxidative stress, proinflammatory cytokines and expression of TNFα, Bax, and p53 genes, and deleterious changes of lymphoid organs, Co-administration of melatonin or turmeric was able to reverse all alterations induced by LL through upregulation of Nrf2/DJ-1 and downregulation of p53/Bax pathways. These data suggest that LL accelerates immunosenescence via oxidative stress and apoptotic pathways. They also demonstrate for the first time that turmeric is comparable to melatonin in boosting the immune function and counteracting the LL-associated immunosenescence. These effects suggest that turmeric supplementation can be used as an inexpensive intervention to prevent circadian disruption-related immunosenescence. However, to validate the effects of turmeric on humans further studies are warranted.

Keywords: Constant light; Gene expression; Immunosenescence; Melatonin; Oxidative stress; Proinflammatory cytokines.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Circadian Rhythm / drug effects
  • Circadian Rhythm / radiation effects
  • Cytokines / blood
  • Down-Regulation / drug effects
  • Down-Regulation / radiation effects
  • Immunosenescence / drug effects*
  • Immunosenescence / radiation effects
  • Light*
  • Male
  • Melatonin / pharmacology*
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects
  • Oxidative Stress / radiation effects
  • Oxidoreductases / metabolism
  • Protein Deglycase DJ-1 / genetics
  • Protein Deglycase DJ-1 / metabolism
  • Rats
  • Signal Transduction / drug effects*
  • Signal Transduction / radiation effects
  • Spleen / drug effects
  • Spleen / metabolism
  • Spleen / pathology
  • Thymus Gland / drug effects
  • Thymus Gland / metabolism
  • Thymus Gland / pathology
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Up-Regulation / drug effects
  • Up-Regulation / radiation effects
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antioxidants
  • Cytokines
  • NF-E2-Related Factor 2
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Oxidoreductases
  • Protein Deglycase DJ-1
  • Melatonin