Adult stem cells, particularly those resident in tissues with little turnover, are largely quiescent and only activate in response to regenerative demands, while embryonic stem cells continuously replicate, suggesting profoundly different regulatory mechanisms within distinct stem cell types. In recent years, evidence linking metabolism, mitochondrial dynamics, and protein homeostasis (proteostasis) as fundamental regulators of stem cell function has emerged. Here, we discuss new insights into how these networks control potency, self-renewal, differentiation, and aging of highly proliferative embryonic stem cells and quiescent adult stem cells, with a focus on hematopoietic and muscle stem cells and implications for anti-aging research.

We thank Dr. E. Perdiguero for design and advice in artwork. P.M.-C. is supported by MINECO (SAF2015-67369-R, María de Maeztu Program for Units of Excellence to UPF [MDM-2014-0370], Severo Ochoa Program for Centers of Excellence to CNIC [SEV-2015-0505]), Convenio UPF-CNIC, ERC-741538, AFM, E-Rare/Eranet, MDA, Fundació Marató-TV3, and DPPE. P.S.-V. is supported by the Glenn Foundation for Medical Research. The authors apologize for work not being mentioned owing to space restrictions.