This paper on Trends in Cell Biology has been yesterday by Research Group on Stem Cell Aging, Leibniz Institute on Aging – Fritz Lipmann Institute (FLI), Beutenbergstr. 11, 07745 Jena, Germany with the following highlights:

• The quiescence stage of stem cells has beneficial and adverse effects on stem cell aging.
• Stem cell quiescence delays stem cell aging by reducing DNA replication, metabolic activity, gene transcription, and mRNA translation, since all of these activities are accompanied by induction of molecular damage.
• Stem cell quiescence comes at the cost of impaired expression of repair factors in quiescence and increased vulnerability in response to stem cell activation requiring the concerted and faithful activation of multiple molecular circuits controlling biosynthetic processes, repair, and metabolic activity.
• Aging-associated increases in stem cell-intrinsic accumulation of molecular damage as well as stem cell-extrinsic alterations (e.g., chronic inflammation, niche cell defects) contribute to the deregulation of quiescence maintenance and increasing vulnerability during exit from quiescence.
• Epigenetic alterations occur during aging in quiescent and activated stem cells and lead to aberrant expression of developmental genes resulting in alterations of quiescence maintenance, self-renewal, and differentiation.
• In conclusion, quiescence protects stem cells against molecular damage but comes at the cost of aging-associated failure in the correct regulation of quiescence maintenance and exit, thus increasing the vulnerability of stem cells during aging.

Stem cells are required for lifelong homeostasis and regeneration of tissues and organs in mammals, but the function of stem cells declines during aging. To preserve stem cells during life, they are kept in a quiescent state with low metabolic and low proliferative activity. However, activation of quiescent stem cells – an essential process for organ homeostasis/regeneration – requires concerted and faithful regulation of multiple molecular circuits controlling biosynthetic processes, repair mechanisms, and metabolic activity. Thus, while protecting stem cell maintenance, quiescence comes at the cost of vulnerability during the process of stem cell activation. Here we discuss molecular and biochemical processes regulating stem cells’ maintenance in and exit from quiescence and how age-related failures of these circuits can contribute to organism aging.