Effects of calorie restriction on mesenchymal stem cells

INTRODUCTION: Calorie restriction (CR) is the most effective way known to extend the lifespan of various organisms including yeast, worms, rodents and monkeys. It has been proved that CR could extend lifespan by inducing SIRT1 expression. SIRT1 is an enzyme with NAD-dependent histone deacetylase activity, and the expression of SIRT1 plays an important role in energy metabolism by regulating the activities of various transcription factors. Mesenchymal stem cells (MSCs) possess unique self-renewal and multi-lineage differentiation capabilities and they are able to replenish a variety of specific cell types. As stem cell aging advances, the activity of a tumor suppressor, p16, increases and modulate stem cell function as a principal mediators of cellular senescence. The purpose of this study is to elucidate the effects of calorie restriction on MSCs and the molecular mechanisms involved. We hypothesize that calorie restriction negatively regulates p16 and positively regulates SIRT1 expression to maintain stemness in bone marrow-derived MSCs.