Stem Cell Ageing and Apoptosis

Abstract

Ageing has been defined as the process of deterioration of many body functions over the lifespan of an individual. In spite of the number of different theories about ageing, there is a general consensus in identifying ageing effects in a reduced capacity to regenerate injured tissues or organs and an increased propensity to infections and cancer. In recent years the stem cell theory of ageing has gained much attention. Adult stem cells residing in mammalian tissues are essential for tissue homeostasis and repair throughout adult life. With advancing age, the highly regulated molecular signalling necessary to ensure proper cellular, tissue, and organ homeostasis loses coordination and leads, as a consequence, to a compromised potential of regeneration and repair of damaged cells and tissues. Although a complete comprehension of the molecular mechanisms involved in stem cell ageing and apoptosis is far to be reached, recent studies are beginning to unravel the processes involved in stem cell ageing, particularly in adult skeletal muscle stem cells, namely satellite cells. Thus, the focus of this review is to analyse the relationship between stem cell ageing and apoptosis with a peculiar attention to human satellite cells as compared to haematopoietic stem cells. Undoubtedly, the knowledge of age-related changes of stem cells will help in understanding the ageing process itself and will provide novel therapeutic challenges for improved tissue regeneration.

CD44 standard and CD44v10 isoform expression on leukemia cells distinctly influences niche embedding of hematopoietic stem cells

“…Thus, it appears that EL4 and EL4-v10 can exert apoptosis promoting as well as protecting effects on BM-Str-embedded HSC, where we speculated that, besides protein interactions, additionally exosomal miRNA might be involved [80,81]. Though the question on the impact of EL4/EL4-v10 and IM7 on the regulation of adult HSC apoptosis resistance, which is still disputed [82,83], requires further elaboration, it is obvious that HSC apoptosis protection is not exclusively regulated via CD44 and also that it is not merely initiated by upregulation of the PI3K/Akt pathway.…”

Regulation of Satellite Cell Function in Sarcopenia

“…Satellite cells that are isolated from sarcopenic muscles from old rodents and humans have a greater propensity for apoptosis and greater levels of apoptotic signaling proteins (Fulle et al, 2012, 2013). Not only can apoptosis signaling target mature post mitotic nuclei for elimination, but satellite cells and their daughter cells that are activated as part of a hypertrophic adaptation to a loading stimulus, can be targets for elimination as well (Alway and Siu, 2008).…”

“…Part of the improvement in apoptotic signaling in activated satellite cells may be due to an upregulation of antioxidants and a reduction of oxidative stress and/or inflammation after nutraceutical treatments including resveratrol (Jackson et al, 2010, 2011; Ryan et al, 2010) and green tea catechins (Ota et al, 2011; Wang et al, 2011; Andrade and Assuncao, 2012; Wu et al, 2012; Haramizu et al, 2013). Given the propensity for apoptosis to occur in satellite cells isolated from old hosts including humans (Fulle et al, 2012, 2013), further investigations into the potential for nutraceuticals to improve satellite cell function in aging are warranted. Together these data support the idea that reducing the systemic (and perhaps also the satellite cell niche) signaling for apoptosis, may promote better survival of satellite cells and their daughter cells in muscles of old animals, and this may contribute to improved muscle recovery after periods of disuse (e.g., hospitalization) and reduce the effects of sarcopenia in the elderly.…”

Age-dependent alteration in muscle regeneration: the critical role of tissue niche

“…Several factors might be involved: (1) reduced number and altered proliferative potential of satellite cells (Schultz and Lipton 1982; Gibson and Schultz 1983; McGeachie and Grounds 1995), (2) telomere shortening in satellite cells (Renault et al 2000), (3) reduced innervations of senescent muscle (Larsson 1982; Larsson and Ansved 1995), (4) increased fibrotic tissue (Marshall et al 1989), (5) altered expression and concentration of systemic, as well as local growth factors and cytokines (Barton-Davis et al 1998; Yablonka-Reuveni et al 1999; Chakravarthy et al 2000; Grounds 2002; Cevenini et al 2010), (6) activation of apoptotic pathways (Fulle et al 2012). …”

“…Recent studies also suggest that apoptosis might be another mechanism involved in sarcopenia (Fulle et al 2012; Marzetti et al 2012). Compared with young animals, a significant increase in muscle cell apoptosis coupled with a decrease in gastrocnemius muscles weight and muscle fiber cross-sectional area, of both fast and slow fiber types, was noted in old mice (Kovacheva et al 2010; Sinha-Hikim et al 2013a).…”