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KMID : 0606920170250050511
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Biomolecules & Therapeutics
2017 Volume.25 No. 5 p.511 ~ p.518
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Aquatide Activation of SIRT1 Reduces Cellular Senescence through a SIRT1-FOXO1-Autophagy Axis
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Lim Chae-Jin
Lee Yong-Moon
Kang Seung-Goo
Lim Hyung-W.
Shin Kyong-Oh
Jeong Se-Kyoo
Huh Yang-Hoon
Choi Su-In
Kor Myung-Ho
Seo Ho-Seong
Park Byeong-Deog
Park Kee-Don
Ahn Jeong-Keun
Uchida Yoshikazu
Park Kyung-Ho
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Abstract
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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-β-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.
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KEYWORD
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Cutaneous cellular senescence, UV irradiation, Aquatide, SIRT1, Autophagy
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