Stems Cells and the Pathways to Aging and Cancer

Immune Disease Institute, Harvard Stem Cell Institute, and the Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Cell (Impact Factor: 32.24). 03/2008; 132(4):681-96. DOI: 10.1016/j.cell.2008.01.036
Source: PubMed


The aging of tissue-specific stem cell and progenitor cell compartments is believed to be central to the decline of tissue and organ integrity and function in the elderly. Here, we examine evidence linking stem cell dysfunction to the pathophysiological conditions accompanying aging, focusing on the mechanisms underlying stem cell decline and their contribution to disease pathogenesis.

6 Reads
    • "Moreover, genetically predisposed organisms are more susceptible to develop bowel diseases or cancers upon chronic infection of the digestive tract (Garrett et al., 2010; Apidianakis and Rahme, 2011; Christofi and Apidianakis, 2013). Aging is also characterized by an overall decline of the intestinal immune function and tissue homeostasis maintenance that in turn can affect lifespan due to the occurrences of diseases (failure of nutrient absorption, susceptibility to infection and superinfections, cancers, etc…), especially in humans whose average lifespan lengthens (DeVeale et al., 2004; Rossi et al., 2008; Biteau et al., 2008, 2010; Alper, 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The digestive tract is subjected to many aggressions throughout animal life. Since disruptions of gut physiology impact on animal fitness and survival, maintenance of gut integrity and functionality is essential for the individual. Over the last 40 years, research on rodents has aimed at understanding how cellular homeostasis of the digestive tract is maintained when challenged with disruptions. Following the discovery of stem cells in the digestive tract of Drosophila, a flurry of studies made an important contribution to our understanding of how the proliferation and the differentiation of these cells are controlled and participate in the renewal of the digestive tract. Insights into these mechanisms in Drosophila have revealed many similarities with mammalian intestinal stem cells. For instance, the highly conserved EGFR, JAK/STAT, Wingless/Wnt, Hedgehog, Integrins, BMP/TGFβ, Hippo and Insulin pathways all participate in adult intestinal cellular homeostasis. Here, we provide a literature review of recent advances in the field highlighting the adult Drosophila midgut as a convenient model for dissecting mechanisms involved in the maintenance of the cellular homeostasis of the digestive tract in conventionally reared conditions. In addition, we shed light on recently published data putting Drosophila forward as a genetic tool to decipher the mechanisms underlying intestinal diseases and intestinal tumour progression.
    Histology and histopathology 10/2014; 30(3). DOI:10.14670/HH-30.277 · 2.10 Impact Factor
    • "Tissue homeostasis and regenerative capacity are nowadays considered to be related to the stem cell pool present in every tissue. For this reason, when an organism undergoes unfavourable physiopathological conditions the reduction in stem cells number and/or function may develop[1718]. However, the correlation between organism aging and cell senescence remains controversial despite decades of studies[161920]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Adult mesenchymal stem cells, specifically adipose-derived stem cells have self-renewal and multiple differentiation potentials and have shown to be the ideal candidate for therapeutic applications in regenerative medicine, particularly in peripheral nerve regeneration. Adipose-derived stem cells are easily harvested, although they may show the effects of aging, hence their potential in nerve repair may be limited by cellular senescence or donor age. Cellular senescence is a complex process whereby stem cells grow old as consequence of intrinsic events (e.g., DNA damage) or environmental cues (e.g., stressful stimuli or diseases), which determine a permanent growth arrest. Several mechanisms are implicated in stem cell senescence, although no one is exclusive of the others. In this review we report some of the most important factors modulating the senescence process, which can influence adipose-derived stem cell morphology and function, and compromise their clinical application for peripheral nerve regenerative cell therapy.
    Neural Regeneration Research 09/2014; 9(1):10-5. DOI:10.4103/1673-5374.125324 · 0.22 Impact Factor
  • Source
    • "The molecular mechanisms responsible for age-dependent decline in HSC self-renewal are complex and many factors have been implicated (Van Zant & Liang, 2003; Chambers & Goodell, 2007; Rossi et al., 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The age-dependent decline in the self-renewal capacity of stem cells plays a critical role in aging, but the precise mechanisms underlying this decline are not well understood. By limiting proliferative capacity, senescence is thought to play an important role in age-dependent decline of stem cell self-renewal, although direct evidence supporting this hypothesis is largely lacking. We have previously identified the E3 ubiquitin ligase Smurf2 as a critical regulator of senescence. In this study, we found that mice deficient in Smurf2 had an expanded hematopoietic stem cell (HSC) compartment in bone marrow under normal homeostatic conditions, and this expansion was associated with enhanced proliferation and reduced quiescence of HSCs. Surprisingly, increased cycling and reduced quiescence of HSCs in Smurf2-deficient mice did not lead to premature exhaustion of stem cells. Instead, HSCs in aged Smurf2-deficient mice had a significantly better repopulating capacity than aged wild-type HSCs, suggesting that decline in HSC function with age is Smurf2 dependent. Furthermore, Smurf2-deficient HSCs exhibited elevated long-term self-renewal capacity and diminished exhaustion in serial transplantation. As we found that the expression of Smurf2 was increased with age and in response to regenerative stress during serial transplantation, our findings suggest that Smurf2 plays an important role in regulating HSC self-renewal and aging.
    Aging cell 02/2014; 13(3). DOI:10.1111/acel.12195 · 6.34 Impact Factor
Show more

Similar Publications

Preview (2 Sources)

6 Reads
Available from