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.
Autophagy ; Cell Aging* ; Fibroblasts ; Humans ; Skin ; Skin Aging

BACKGROUND/AIMS: We aimed to investigate whether the current indications for curative endoscopic resection (ER) of gastric cancer (GC) can be applied to GC caused by adenoma. Additionally, we attempted to identify factors predictive of lesions subsequently found in addition to the expanded indications for ER. METHODS: We retrospectively analyzed 342 patients diagnosed with GC caused by adenoma who underwent ER at a single tertiary center between February 2011 and December 2014. The gross whole tumor size was measured using the endoscopically resected specimen. The microscopic whole tumor size was measured using mapping paper. The estimated cancer size was calculated using the microscopic whole tumor size and the square root of the carcinoma component. RESULTS: A gross whole tumor size ≥3 cm, carcinoma component ≥35%, and gross ulceration were predictive of lesions other than the expanded indications for ER. The overall rate of lymph node metastasis was 0.3% (1/327), which only occurred in one patient with a lesion other than the expanded indications (4.5%, 1/22). CONCLUSIONS: The current indications for curative ER in GC can be applied to GC caused by adenoma. In cases suspected of having lesions other than the expanded indications, patients should be cautiously selected for ER to reduce the risk of an inappropriate procedure.
Adenocarcinoma ; Adenoma* ; Endoscopy ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Retrospective Studies ; Stomach Neoplasms* ; Ulcer