Nicotinamide phosphoribosyltransferase delays cellular senescence by upregulating SIRT1 activity and antioxidant gene expression in mouse cells.
Genes Cells
; 22(12): 982-992, 2017 Dec.
Article
en En
| MEDLINE
| ID: mdl-29178516
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Regulación de la Expresión Génica
/
Citocinas
/
Senescencia Celular
/
Nicotinamida Fosforribosiltransferasa
/
Sirtuina 1
/
Antioxidantes
Límite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Genes Cells
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2017
Tipo del documento:
Article
País de afiliación:
Japón