title: Nampt Expression Decreases Age-Related Senescence in Rat Bone Marrow Mesenchymal Stem Cells by Targeting Sirt1.
abstract: Senescence restricts the development of applications involving mesenchymal stem cells (MSCs) in research fields, such as tissue engineering, and stem cell therapeutic strategies. Understanding the mechanisms underlying natural aging processes may contribute to the development of novel approaches to preventing age-related diseases or slowing individual aging processes. Nampt is a rate-limiting NAD biosynthetic enzyme that plays critical roles in energy metabolism, cell senescence and maintaining life spans. However, it remains unknown whether Nampt influences stem cell senescence. In this study, the function of Nampt was investigated using a rat model of natural aging. Our data show that Nampt expression was significantly lower in MSCs obtained from aged rats than in those obtained from young rats during physiological aging. Reducing the level of Nampt in aged MSCs resulted in lower intracellular concentrations of NAD+ and downregulated Sirt1 expression and activity. After the Nampt inhibitor FK866 was added, young MSCs were induced to become aged cells. The enhanced senescence was correlated with NAD+ depletion and Sirt1 activity attenuation. In addition, Nampt overexpression attenuated cell senescence in aged MSCs. Our findings provide a new explanation for the mechanisms underlying stem cell senescence and a novel target for delaying stem cell senescence and preventing and treating age-related diseases.
authors.affiliation: The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, China.|Department of Pathology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Cao
authors.initials: C
authors.lastname: Ma
authors.affiliation: The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, China.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Pi
authors.affiliation: The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.affiliation: The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, China.
authors.forename: Yingai
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Center for Advanced Reconstruction of Extremities (C.A.R.E.), Sahlgrenska University Hospital, Mölndal, Sweden.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Li
authors.affiliation: The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, China.
authors.forename: Xu
authors.initials: X
authors.lastname: He
mesh_terms: D000178:Acrylamides / Q000494:pharmacology; D000367:Age Factors; D000375:Aging / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism*; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology*; D015536:Down-Regulation / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D054409:Nicotinamide Phosphoribosyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000178:Acrylamides; C480543:N-(4-(1-benzoylpiperidin-4-yl)butyl)-3-(pyridin-3-yl)acrylamide; D010880:Piperidines; D054409:Nicotinamide Phosphoribosyltransferase; D056564:Sirtuin 1