Over‐expression of Nicotinamide phosphoribosyltransferase in mouse cells confers protective effect against oxidative and ER stress‐induced premature senescence
Document Type
Article
Publication Date
1-1-2020
Abstract
A main feature of aged organisms is the accumulation of senescent cells. Accumulated senescent cells, especially stress-induced premature senescent cells, in aged organisms lead to the decline of the regenerative potential and function of tissues. We recently reported that the over-expression of NAMPT, which is the rate-limiting enzyme in mammalian NAD+ salvage pathway, delays replicative senescence in vitro. However, whether Nampt-overexpressing cells are tolerant of stress-induced premature senescence remains unknown. Here, we show that primary mouse embryonic fibroblasts derived from Nampt-overexpressing transgenic mice (Nampt Tg-MEF cells) possess resistance against stress-induced premature senescence in vitro. We found that higher oxidative or endoplasmic reticulum (ER) stress is required to induce premature senescence in Nampt Tg-MEF cells compared to wild-type cells. Moreover, we found that Nampt Tg-MEF cells show acute expression of unfolded protein response (UPR)-related genes, which in turn would have helped to restore proteostasis and avoid cellular senescence. Our results demonstrate that NAMPT/NAD+ axis functions to protect cells not only from replicative senescence, but also from stress-induced premature senescence in vitro. We anticipate that in vivo activation of NAMPT activity or increment of NAD+ would protect tissues from the accumulation of premature senescent cells, thereby maintaining healthy aging. © 2020 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd
Keywords
ER stress, NAD+, NAMPT, oxidative stress, premature senescence
Divisions
cebar
Funders
JSPS KAKENHI Grant Number 17K08569,Takeda Science Foundation,Directorate of Higher Education, The Ministry of Education and Culture of Indonesia, grant year 2014 (BPPLN-DIKTI, 2014)
Publication Title
Genes to Cells
Volume
25
Issue
8
Publisher
Wiley