Caloric restriction rejuvenates aged adult stem cells: From mechanisms to interventions

Adult stem cells are essential for maintaining tissue homeostasis and facilitating tissue repair. The ability of aged stem cells to generate functional progeny declines, which is closely associated with the onset and progression of age-related diseases. The aging of adult stem cells in various tissues is regulated jointly by local microenvironments (stem cell niches) and systemic factors. Caloric restriction (CR), a widely studied anti-aging strategy, has been demonstrated to rejuvenate aged stem cells by directly targeting the stem cells themselves or their niches across multiple tissues including blood, intestine, brain, and muscle. In this article, the anti-aging effects of different CR-based dietary strategies are described and compared, and the molecular mechanisms by which CR rejuvenates aged stem cells are discussed, with a particular focus on the highly conserved nutrient-sensing/growth-promoting network centered around mammalian target of rapamycin (mTOR), while also elaborating on the key role of stem cell niches in this process. Finally, the advantages and disadvantages of caloric restriction mimetics (CRMs) relative to CR are compared, the prospects and limitations of CR-mediated anti-aging effects are discussed, and key directions for future research are identified.