Fig. 1.

Nutrient sensing by the mTOR, AMPK, and PPAR signaling pathways. When growth factors and nutrients are abundant, mTORC1 is active and promotes anabolic processes, proliferation and differentiation, while AMPK and PPAR signaling are suppressed. When nutrients become scarce, AMPK is activated and mTORC1 becomes inhibited, resulting in increased catabolic processes and autophagy. At the same time, PPAR mediated fatty acid oxidation and ketogenesis are induced and enhance stem cell function, particularly in intestinal stem cells. With aging, fatty acid oxidation may be limited and mTORC1 activity may be hyperactivated leading to functional decline in stem cells. Interventions such as rapamycin aim to inhibit mTORC1, and treatments such as PPAR agonists or dietary regiments that enhance fatty acid oxidation and ketogenesis may improve age-associated decline in stem cell function, particularly in the gut