Downregulation of KLF14 accelerated cellular senescence and aging

Abstract

Aging has been considered as a risk factor in many diseases, thus, comprehensively understanding the cellular and molecular mechanisms of delayed aging is important. Here we investigated whether KLF14 is a suppressor of cellular senescence and aging. In our research, KLF14 levels significantly decreased not only in the serum and lymphocytes of healthy people but also in the cells and tissues of mice with aging. We performed in vitro and in vivo experiments on cells and mice to reveal the function of KLF14 in aging. KLF14 deficiency facilitates cellular senescence and aging-related pathologies in C57BL/6 mice, whereas KLF14 overexpression attenuates cellular senescence. Mechanistically, KLF14 delays aging by binding to the POLD1 promoter to positively regulate POLD1 expression. Remarkably, cellular senescence mediated by KLF14 downregulation could be alleviated by POLD1expression. In addition, perhexiline, an agonist of KLF14, could delay cellular senescence and aging-related pathologies in SAMP8 mice by inducing POLD1 expression, as perhexiline could enhance the effect of KLF14’s transcription activation to POLD1 by elevating the binding level of KLF14 to the POLD1 promoter. Our data indicate that KLF14 might be a critical element in aging by upregulating POLD1 expression, indicating that the activation of KLF14 may delay aging and aging-associated diseases.

Gastric epithelial neoplasm of fundic-gland mucosa lineage: representative of the low atypia differentiated gastric tumor and Ki67 may help in their identification

“…According to the WHO classification, the depth of invasion differentiates between OGA and GA-FG [9]. Based on the Japanese diagnostic criteria, despite showing low-grade atypia and invading the submucosal layer, many stomach neoplasms are diagnosed as invasive carcinomas in the absence of an obvious desmoplastic response [2,18,19]. Thus, Japanese scholars have proposed that OGA is the intramucosal stage of GA-FG, and OGA and GA-FG The identification of OGA and GA-FG as intramucosal adenomas or low-grade gastric adenocarcinomas relies on whether the pathologist uses the Western or Japanese diagnostic criteria.…”