The systemic milieu as a mediator of dietary influence on stem cell function during ageing

The regenerative decline of organisms during ageing is linked to the reduced proliferative activity, impaired function and exhaustion of tissue-specific stem and progenitor cells. Studies using heterochronic parabiosis, involving the surgical attachment of young and old organisms so that they share a common vascular system, have revealed that the systemic environment has a profound effect on stem cell function. In particular, specific youthful rejuvenating circulatory factors reverse age-related declines in stem cell function, whereas the old milieu contains inhibitory factors that impede stem cell function in young animals. Similarly, the effects of certain dietary interventions, namely calorie restriction, also induce a more youthful cellular and molecular phenotype in ageing stem cells throughout the body. Further to this, there are key molecular pathways involved in translating the availability of nutrients into altered stem cell function, including signalling in the insulin and insulin-like growth factor and mechanistic target of rapamycin (mTOR) pathways. In this review, we discuss the potential role of dietary interventions to promote a more rejuvenating systemic milieu in order to enhance stem cell function and promote healthy ageing.