Quercetin, caffeic acid and resveratrol regulate circadian clock genes and aging-related genes in young and old human lung fibroblast cells

  • Yoshinori OkadaEmail author
  • Mizue Okada
Original Article


The circadian timing system of mammals is synchronized in concert with a central clock, but is also influenced by additional stimuli, including nutrients. However, little research has been done on polyphenols other than resveratrol and there seem to be no studies on their influence on young and old cells. The purpose of this study was to analyse the potential effects of quercetin, caffeic acid, and resveratrol on young and old fibroblast cells in the expressions of different clock genes and aging-related genes, and further investigate the mechanism. The mRNA expression of different clock genes and aging-related genes was assessed by quantitative real-time PCR. The protein levels of clock genes (BMAL1, PER1 and SIRT1) and glucocorticoid receptor α (GRα) were assessed by ELISA. Quercetin and caffeic acid in old fibroblast cells showed higher clock gene expression than resveratrol, quercetin increased Sirt1 expression, and caffeic acid increased Sirt6 expression indicating the possibility of an anti-aging effect. Also, quercetin and caffeic acid showed higher clock-controlled gene (Sirt1 and NR1D1) expression than resveratrol in young fibroblast cells. It appears that caffeic acid acts on NRF2 expression, and in turn to the actions of GRα, GDF11, Sirt1, and Sirt6. Regarding the increased expression of Per1, the activation effect on NR1D1 was confirmed only for caffeic acid in young fibroblast cells. Our results have confirmed the interplay of the circadian clock genes and cellular aging.


Quercetin Caffeic acid Circadian clock genes Resveratrol NR1D1 NRF2 



Research was supported by the Grant-in-Aid for Scientific Research (Grant No. 17K00863) from the Japanese Ministry of Education, Culture, Sports, Science and Technology We thank Ms. Wanda Miyata for help with critical review.

Compliance with ethical standards

Conflict of interest

Authors have no potential conflict of interest.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Laboratory on Ageing & Health Management, Graduate School of Nursing & HealthAichi Prefectural University, Tohgoku, Kamishidami, MoriyamaNagoyaJapan
  2. 2.Nutrition Section, Ageing and Nutrition ResearchYms LaboratoryGifuJapan

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