Relationships between stem cell exhaustion, tumour suppression and ageing.
Ageing is a complex process characterised by a variety of disorders associated with general organismal decline and an inability to maintain tissue homoeostasis. As described in this review, recent studies indicate that ageing may be caused, in part, by the depletion of stem and progenitor cells that govern tissue renewal. The potential causes of stem and progenitor cell attrition are numerous; however, a commonly accepted theory is that these cells are lost as a result of naturally occurring DNA damage and the obligate checkpoint responses that follow. Failure to launch appropriate responses to DNA damage is strongly associated with cancer initiation and progression. Therefore, it is at this nexus, the response to DNA damage, that an important organismal fate may be determined: to degrade regenerative potential for the purpose of preventing cancer. According to this viewpoint, ageing may be the unfortunate mark of successful cancer suppression in stem cells and other cell types. In this review, we will describe how degeneration of tissue renewal capacity links ageing and cancer suppression.
Ruzankina
Y
Y
1Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 421 Curie Blvd., Philadelphia, PA 19104-6160, USA.
Brown
E J
EJ
D000375:Aging / Q000502:physiology*; D000818:Animals; D004249:DNA Damage; D006801:Humans; D009369:Neoplasms / Q000517:prevention & control*; D012038:Regeneration; D013234:Stem Cells / Q000378:metabolism*