Ascorbic acid inhibits senescence in mesenchymal stem cells through ROS and AKT/mTOR signaling

Abstract

Mesenchymal stem cell (MSC) aging seriously affects its function in stem cell transplantation for treatment. Extensive studies have focused on how to inhibit senescence in MSCs. However, the mechanism of senescence in MSC was not clear. In this study, we used D-galactose to induce MSC aging. Then we found that the number of aging cells was increased compared with untreated MSCs. We discovered that ascorbic acid could inhibit the production of reactive oxygen species (ROS) and activation of AKT/mTOR signaling in MSCs caused by D-galactose. Especially, when treated together with a ROS scavenger or AKT inhibitor, the senescent cells were obviously decreased in D-galactose-induced MSCs. Taken together, we identify that ascorbic acid owns the potential to inhibit the senescence of MSCs through ROS and Akt/mTOR signaling. Together, our data supports that ascorbic acid can be used to prevent MSCs from senescence, which can enhance the efficiency of stem cell transplantation in the clinic.

Vitamin C restores ovarian follicular reservation in a mouse model of aging

“…Along with the effects of vitamin C on vascularization, metabolism, and inflammation mentioned above, it has also antioxidant effects. In this regard, vitamin C can postpone aging in MSCs via prevention of the ROS production and AKT/mTOR signaling [21]. Arab et al [20] found that antioxidant effect of ascorbic acid could ameliorate increased oxidative stress induced by malathion in the rats ovary.…”

“…Application of free radicals scavengers can protect ovary from the damage of oxidative stress [181920]. Vitamin C (L-ascorbic acid) is a natural antioxidant scavenging ROS effectively [2122]. In addition, useful effects of vitamin C on metabolism, collagen synthesis, vasculogenesis, aging, cell proliferation, and differentiation has been reported previously [21222324].…”

“…Vitamin C (L-ascorbic acid) is a natural antioxidant scavenging ROS effectively [2122]. In addition, useful effects of vitamin C on metabolism, collagen synthesis, vasculogenesis, aging, cell proliferation, and differentiation has been reported previously [21222324]. Although, so far, several studies have investigated the role of vitamin C in combination with other antioxidants on female infertility [51925], there are scarcely data regarding to the effect of vitamin C alone on ovarian aging.…”

Senescent mesenchymal stem/stromal cells and restoring their cellular functions

“…Additional potential regulators: The AKT pathway plays an important role in the rejuvenation of features and functions of aged MSCs. This pathway can act via ERBB4/PI3K/AKT[ 112 ], lactoferrin/AKT[ 113 ], Vc/AKT/mTOR[ 114 ], and fucoidan/FAK-Akt-TWIST axes[ 115 ]. Administration of rapamycin, an inhibitor of the mTOR signaling pathway, raised the expression level of NANOG, postponed replicative arrest, and enhanced the lifespan increment of BM-MSCs[ 116 ].…”

Identification of senescent cells in multipotent mesenchymal stromal cell cultures: Current methods and future directions

“…Activation of autophagy through Sirtuin mobilization [143,156,158] Ascorbic acid Reduction in ROS levels and inhibition of the AKT/mTOR signalling [159] C1q and tumour necrosis factor-related protein 9 (CTRP9)…”