Metabolic Regulation: A Potential Strategy for Rescuing Stem Cell Senescence

Abstract

Stem cell senescence and exhaustion are closely related to organ failure and individual aging, which not only induces age-related diseases, but also hinders stem cell applications in regenerative medicine. Thus, it's imminent to find effective ways to delay and retrieve stem cell senescence. Metabolic abnormalities are one of the main characteristics of age-associated declines in stem cell function. Understanding the underlying mechanisms may reveal potential strategies for ameliorating age-associated phenotypes and treating age-related diseases. This review focuses on recent advances in the association between metabolism including glucose, lipid, glutamine and NAD⁺ metabolism and stem cell senescence, as well as the other properties like proliferation and differentiation. Layers of studies are summarized to demonstrate how metabolism varies in senescent stem cells and how metabolic reprogramming regulates stem cell senescence. Additionally, we mentioned some recent progress in therapeutic strategies to rejuvenate dysfunctional aged stem cells. Finally, a brief conclusion about the prospect of metabolic regulation as a potential strategy for rescuing stem cell senescence is displayed. Stem cell senescence is induced by the metabolic reprogramming. The metabolic alterations of glucose, lipid, glutamine and NAD⁺ can conversely facilitate or inhibit stem cell senescence. Glycolysis, OXPHOS and PPP are all attenuated. But gluconeogenesis alterations still remain unclear. In lipid metabolisms, both FAO and DNL are suppressed. As for the glutamine metabolism, stem cells' dependence on glutamine is enhanced. Last, NAD⁺ metabolism undergoes a down-regulated synthesis and up-regulated consumption. All these alterations can be potential targets for reversing stem cell senescence.

Keywords: NAD+ metabolism; age-related diseases; glucose metabolism; glutamine metabolism; lipid metabolism; stem cell senescence.