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Aquatide Activation of SIRT1 Reduces Cellular Senescence through a SIRT1-FOXO1-Autophagy Axis

  • Lim, Chae Jin (Department of Microbiology and Molecular Biology, School of Bioscience and Biotechnology, Chungnam National University) ;
  • Lee, Yong-Moon (College of Pharmacy Chungbuk National University) ;
  • Kang, Seung Goo (Division of Biomedical Convergence and Institute of Bioscience & Biotechnology, Kangwon National University) ;
  • Lim, Hyung W. (Gladstone Institute of Virology and Immunology, Gladstone Institute of Neurological Disease, School of Medicine, Department of Neurology, University of California) ;
  • Shin, Kyong-Oh (College of Pharmacy Chungbuk National University) ;
  • Jeong, Se Kyoo (Department of Cosmetic Science, Seowon University) ;
  • Huh, Yang Hoon (Korea Basic Science Institute) ;
  • Choi, Suin (Korea Basic Science Institute) ;
  • Kor, Myungho (Peptide R&D Center, Incospharm Corporation) ;
  • Seo, Ho Seong (Radiation Biotechnology Research Division, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute) ;
  • Park, Byeong Deog (NeoPharm USA) ;
  • Park, Keedon (Peptide R&D Center, Incospharm Corporation) ;
  • Ahn, Jeong Keun (Department of Microbiology and Molecular Biology, School of Bioscience and Biotechnology, Chungnam National University) ;
  • Uchida, Yoshikazu (Department of Dermatology, School of Medicine, University of California, Northern California Institute for Research and Education, Veterans Affairs Medical Center) ;
  • Park, Kyungho (Department of Dermatology, School of Medicine, University of California, Northern California Institute for Research and Education, Veterans Affairs Medical Center)
  • Received : 2017.06.04
  • Accepted : 2017.06.15
  • Published : 2017.09.01

Abstract

Ultraviolet (UV) irradiation is a relevant environment factor to induce cellular senescence and photoaging. Both autophagy- and silent information regulator T1 (SIRT1)-dependent pathways are critical cellular processes of not only maintaining normal cellular functions, but also protecting cellular senescence in skin exposed to UV irradiation. In the present studies, we investigated whether modulation of autophagy induction using a novel synthetic SIRT1 activator, heptasodium hexacarboxymethyl dipeptide-12 (named as Aquatide), suppresses the UVB irradiation-induced skin aging. Treatment with Aquatide directly activates SIRT1 and stimulates autophagy induction in cultured human dermal fibroblasts. Next, we found that Aquatide-mediated activation of SIRT1 increases autophagy induction via deacetylation of forkhead box class O (FOXO) 1. Finally, UVB irradiation-induced cellular senescence measured by $SA-{\beta}-gal$ staining was significantly decreased in cells treated with Aquatide in parallel to occurring SIRT1 activation-dependent autophagy. Together, Aquatide modulates autophagy through SIRT1 activation, contributing to suppression of skin aging caused by UV irradiation.

Keywords

References

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