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Genes Cells. 2017 Dec;22(12):982-992. doi: 10.1111/gtc.12542. Epub 2017 Nov 27.

Nicotinamide phosphoribosyltransferase delays cellular senescence by upregulating SIRT1 activity and antioxidant gene expression in mouse cells.

Author information

1
Laboratory of Gene Regulation Research, Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST), Ikoma, Nara, Japan.
2
Laboratory of Molecular and Cell Genetics, Graduate School of Biological Sciences and Institute for Research Initiatives, Nara Institute of Science and Technology (NAIST), Ikoma, Nara, Japan.

Abstract

Senescent cells accumulate in tissues of aged animals and deteriorate tissue functions. The elimination of senescent cells from aged mice not only attenuates progression of already established age-related disorders, but also extends median lifespan. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in mammalian NAD+ salvage pathway, has shown a protective effect on cellular senescence of human primary cells. However, it still remains unclear how NAMPT has a protective impact on aging in vitro and in vivo. In this study, we found that primary mouse embryonic fibroblast (MEF) cells undergo progressive decline of NAMPT and NAD+ contents during serial passaging before becoming senescent. Furthermore, we showed that constitutive Nampt over-expression increases cellular NAD+ content and delays cellular senescence of MEF cells in vitro. We further found that constitutive Nampt over-expression increases SIRT1 activity, increases the expression of antioxidant genes, superoxide dismutase 2 and catalase and promotes resistance against oxidative stress. These findings suggest that Nampt over-expression in MEF cells delays cellular senescence by the mitigation of oxidative stress via the upregulation of superoxide dismutase 2 and catalase gene expressions by SIRT1 activation.

KEYWORDS:

NAD + ; Nampt; SIRT1; antioxidant genes; cellular senescence

PMID:
29178516
DOI:
10.1111/gtc.12542
[Indexed for MEDLINE]
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