Alterations of Systemic Environment Impair Stem Cell Function during Aging

Aging is associated with a decline in tissue repair and organ regeneration. There is growing evidence that agerelated decline of stem cell function contributes to the failure of organ maintenance and homeostasis, yet it remains to be investigated to what extent this is responsible for the development of age-related pathologies across different organs. In humans, it has been shown that both donor age and recipient age influence patient outcomes in response to hematopoietic stem cell transplantation. In transplantation experiments in mice, both stem cell-intrinsic and -extrinsic defects have been implicated in the age-dependent decline of functional stem cell reserves. During the Else KrÖner-Fresenius Symposium on the Molecular Mechanisms of Adult Stem Cell Aging, several speakers indicated that cell-extrinsic cues play an important role in the function and fate decision of stem cells during aging. Extrinsic factors that can influence stem cell function can be divided into 2 compartments: the cellular niche (microenvironment) and the systemic environment (macroenvironment). Evidence from various model systems demonstrates that both stem cell niche and systemic environment are crucial for the maintenance of functional stem cells during aging. Age-associated alterations in the microenvironment limit stem cell function in various stem cell compartments, such as melanocyte stem cells, intestinal stem cells, spermatogonia, muscle stem cells, and bone marrow stem cells. The impact of the stem microenvironment on stem cell function and maintenance during aging will be discussed by Dr. Geiger in chapter 4. Here, we focus on new concepts presented during the meeting regarding the impact of age-dependent, systemic environmental alterations on stem cell aging.