Relationships between stem cell exhaustion, tumour suppression and ageing

Abstract

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.

Hallmarks of the ageing lung

“…2), which is in contrast to the continuously rising incidences for COPD and IPF. Importantly, such a decline in cancer incidence at an older age has been reported for cancer in general and was initially attributed to the selection of protected ("non-susceptible") individuals, but may rather involve stem cell exhaustion [102,173]. In contrast, the development of progenitor cells into cancer stem cells, which exhibit dysregulated self-renewal and differentiation is well established [163,174,175].…”

BMI1 Confers Radioresistance to Normal and Cancerous Neural Stem Cells through Recruitment of the DNA Damage Response Machinery

“…Unrepaired mutations in DNA or genetic instability can lead to cancer. In turn, substantial evidence suggests that aging is driven by the accumulation of somatic mutations in genomic (and mitochondrial) DNA (Ruzankina and Brown, 2007). Notably, deficiency in DNA DSB repair results in NSC genetic instability, apoptosis, and exhaustion with aging (Sii-Felice et al, 2008a,b).…”

Cellular senescence, ageing and disease

“…Stem cells express telomerase and are unlikely to become senescent in response to telomere shortening (Ruzankina and Brown 2007). However, it may still be possible for stem cells to enter senescence in response to DNA damage (Ruzankina et al 2008), consequently taking up valuable space in stem cell niches (Lynch 2006), reducing the stem cell pool, leading to an age-related loss in regenerative capacity.…”