Objectives There is an age-related decline in mesenchymal stem cells (MSCs) functions and old age have a negative effect on MSCs ageing and proliferation.
To investigate the role of SIRT1, a NAD+ dependent histone deacetylase, in old sourced MSCs senescence and proliferation, we examined the effects of Sirt1 manipulation in Old sourced MSCs.
Methods Primary MSCs from Old rats were treated with sirtinol, a SIRT1 inhibitor, or resveratrol, a SIRT1 activator, respectly. β-galactosidase activity was used to evaluate cell senescenceand CCK8 was used to assay the proliferating situation of MSCs.
Results Comparing to young sourced MSCs, β-galactosidase positive cells increased in old MSCs and cell proliferation was also decreased. Inhibition of SIRT1 by sirtinol increased β-galactosidase positive cellsin Old MSCs and activation of SIRT1 by resveratrol reversed this effect. MSCs proliferation was decreased markedly in sirtinol group and this phenomenon was in a dose-dependent manner. Resveratrol significantly enhance MSCs proliferation also in a dose-dependent manner while resveratrol concentrations greater than 80uM resulted in significantly reduced MSCs viability. ageing marker P16, but not P21, may involved in SIRT1 action. Western blot analysis showed that pERK1/2 was increased in resveratrol group and decreased in sirtinol group, denoting that this pathway may participate in SIRT1 action.
Conclusions SIRT1 significantly influences Old sourced MSCs aging and proliferation, so that manipulate SIRT1 in Old sourced MSCs with chemical substance, resveratrol for example, can meliorate its aging phenotype.