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.

    • "These processes are mediated by tissue-specific stem cells, suggesting that impaired stem cell function may underlie central cellular pathophysiologies associated with aging. Indeed, mounting evidence indicates that degenerative aging-associated changes in adult stem cells are a central driver of many age-related phenotypes (reviewed in Oh et al., 2014; Liu and Rando, 2011; Behrens et al., 2014; Rossi et al., 2008). The mechanistic basis for aging-associated stem cell decline is not completely understood, but numerous studies have shown that loss of polarity (Florian et al., 2012), mitochondrial dysfunction (Bratic and Larsson, 2013), altered autophagy (Warr et al., 2013), replicative stress (Flach et al., 2014), and accrual of DNA damage (Rossi et al., 2007; Rü be et al., 2011; Yahata et al., 2011; Wang et al., 2012; Beerman et al., 2014) all contribute to stem cell aging. "
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    ABSTRACT: Stem cell decline is an important cellular driver of aging-associated pathophysiology in multiple tissues. Epigenetic regulation is central to establishing and maintaining stem cell function, and emerging evidence indicates that epigenetic dysregulation contributes to the altered potential of stem cells during aging. Unlike terminally differentiated cells, the impact of epigenetic dysregulation in stem cells is propagated beyond self; alterations can be heritably transmitted to differentiated progeny, in addition to being perpetuated and amplified within the stem cell pool through self-renewal divisions. This Review focuses on recent studies examining epigenetic regulation of tissue-specific stem cells in homeostasis, aging, and aging-related disease. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Jun 2015 · Cell stem cell
    • "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). "
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    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.
    No preview · Article · Oct 2014 · Histology and histopathology
    • "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]. "
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    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.
    No preview · Article · Sep 2014 · Neural Regeneration Research
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