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.

Pyridine Dinucleotides from Molecules to Man

“…Two hypotheses address the age-related decrease in NAD. First, NAMPT expression decreases with age (127,152,171), which would hamper nicotinamide recovery by the salvage pathway for NAD synthesis. Decreased NAMPT may be a consequence of dysregulated circadian rhythm (171) or redox stress and chronic inflammation associated with aging (105).…”

Low‐intensity pulsed ultrasound activates ERK1/2 and PI3K‐Akt signalling pathways and promotes the proliferation of human amnion‐derived mesenchymal stem cells

“…However, the population of MSCs in bone marrow is low (about 0.001%‐0.01%) and the procedure to obtain bone marrow MSCs (BM‐MSCs) is invasive. Moreover, the number, proliferation ability and differentiation potential of MSCs from bone marrow will decrease as the age of donor increases . Thus, it is necessary to find an alternative source of MSCs.…”

Melatonin Reverses the Loss of Stemness Induced by TNF-α in Human Bone Marrow Mesenchymal Stem Cells through Upregulation of YAP Expression

“…For in vitro generation and origination, the stemness of MSCs can be maintained in the early and middle generations of in vitro growth. However, stemness can experience a significant reduction once a critical time is exceeded [36,37]. Meanwhile, stem cells from different tissue sources have significant differences in their abilities to maintain stemness during in vitro culture.…”