Heterochronic parabiosis for the study of the effects of aging on stem cells and their niche

Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA.
Cell cycle (Georgetown, Tex.) (Impact Factor: 4.57). 06/2012; 11(12):2260-7. DOI: 10.4161/cc.20437
Source: PubMed


Aging is unmistakable and undeniable in mammals. Interestingly, mice develop cataracts, muscle atrophy, osteoporosis, obesity, diabetes and cognitive deficits after just 2-3 postnatal years, while it takes seven or more decades for the same age-specific phenotypes to develop in humans. Thus, chronological age corresponds differently with biological age in metazoan species and although many theories exist, we do not understand what controls the rate of mammalian aging. One interesting idea is that species-specific rate of aging represents a ratio of tissue attrition to tissue regeneration. Furthermore, current findings suggest that the age-imposed biochemical changes in the niches of tissue stem cells inhibit performance of this regenerative pool, which leads to the decline of tissue maintenance and repair. If true, slowing down stem cell and niche aging, thereby promoting tissue regeneration, could slow down the process of tissue and organismal aging. In this regard, recent studies of heterochronic parabiosis provide important clues as to the mechanisms of stem cell aging and suggest novel strategies for enhancing tissue repair in the old. Here we review current literature on the relationship between the vigor of tissue stem cells and the process of aging, with an emphasis on the rejuvenation of old tissues by the extrinsic modifications of stem cell niches.

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    • "There is wide evidence, both in animals models and in humans, the Wnt signaling pathway is down regulated with aging and contributes to the progressive reduction in muscle regeneration and repair capacity (Conboy and Rando, 2012). Wnt proteins are a large family (19 members in humans) of secreted glycoproteins that are highly evolutionary conserved. "
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    ABSTRACT: Aging is associated with a progressive loss of muscle mass and strength and a decline in neurophysiological functions. Age-related neuromuscular junction (NMJ) plays a key role in musculoskeletal impairment that occurs with aging. However, whether changes in the NMJ precede or follow the decline of muscle mass and strength remains unresolved. Many factors such as mitochondrial dysfunction, oxidative stress, inflammation, changes in the innervation of muscle fibers, and mechanical properties of the motor units probably perform an important role in NMJ degeneration and muscle mass and strength decline in late life. This review addresses the primary events that might lead to NMJ dysfunction with aging, including studies on biomarkers, signaling pathways, and animal models. Interventions such as caloric restriction and exercise may positively affect the NMJ through this mechanism and attenuate the age-related progressive impairment in motor function.
    Frontiers in Aging Neuroscience 08/2014; 6:208. DOI:10.3389/fnagi.2014.00208 · 4.00 Impact Factor
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    • "Especially in early, mid, and older adults, stem cells reduced or ceased their growth and regeneration capacities to maintain tissue homeostasis or to reduce cancer development risk in aging tissues (Signer and Morrison 2013). Additionally, the current findings in the literature suggest that such biochemical changes in the stem cell niches are responsible for regenerative declines in older mammalians (Conboy and Rando 2012). The MTT assay results of the present study showed that metabolic and cellular activity of the early and mid adult BM-MSCs decreased, such a decrease in the mitochondrial activity, growth, and metabolic rates of the cells of mammalian tissues can influence the rates of the cellular aging at the later stages of the life (Dillin et al. 2002). "
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    ABSTRACT: Stem cell studies hold enormous potential for development of new therapies for tissue regeneration and repair. Bone marrow mesenchymal stem cells (BM-MSCs) can differentiate into a variety of non-hematopoietic tissues and contribute maintenance of healthy hematopoiesis by providing supportive cellular microenvironment into BM. Here, we investigated age-related differences in BM-MSCs by using attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy and FTIR imaging together with hierarchical clustering as a novel methods to clarify global alterations in the structure and function of macromolecules in characterized BM-MSCs of different aged donors. The results may contribute to identification of age-related new molecular marker(s) to determine the effects of donor age on MSCs. The spectral results reflected that there were significant increases in the concentration of saturated lipids, proteins, glycogen, and nucleic acids in children and adolescent group BM-MSCs when compared to the infants and early and mid adults. The concentration of mentioned macromolecules in adult (early and mid) BM-MSCs were significantly lower than the concentrations in the children and adolescents. These results were attributed to the increase in the proliferation activity in younger BM-MSCs. The distribution of macromolecules into the cells was shown as in the form of chemical maps by FTIR imaging, and the results are in agreement with the ATR-FTIR spectroscopy results. The cellular activity degree was determined by the thiazolyl blue tetrazolium bromide (MTT) proliferation assay to support ATR-FTIR spectroscopy results. BM-MSCs of five different age groups were discriminated by making the hierarchical cluster analysis where the spectral data according to alterations in structure and composition of macromolecules were considered.
    Journal of the American Aging Association 08/2014; 36(4):9691. DOI:10.1007/s11357-014-9691-7 · 3.39 Impact Factor
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    • "In addition, muscle stem (satellite) cells (MuSCs), responsible for dictating skeletal muscle regenerative capacity, display impaired functioning with increasing age (reviewed in Conboy and Rando, 2012). With age, these cells demonstrate a decline in regenerative potential owing to altered cellular proliferation and myogenic differentiation (reviewed in Mann et al., 2011; Conboy and Rando, 2012). As the number of elderly individuals in the United States grows, functional detriments resulting from these age-related declines in skeletal muscle maintenance and healing capacity will increasingly represent an important public health burden. "
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    ABSTRACT: Klotho is a powerful longevity protein that has been linked to the prevention of muscle atrophy, osteopenia, and cardiovascular disease. Similar anti-aging effects have also been ascribed to exercise and physical activity. While an association between muscle function and Klotho expression has been previously suggested from longitudinal cohort studies, a direct relationship between circulating Klotho and skeletal muscle has not been investigated. In this paper, we present a review of the literature and preliminary evidence that, together, suggests Klotho expression may be modulated by skeletal muscle activity. Our pilot clinical findings performed in young and aged individuals suggest that circulating Klotho levels are upregulated in response to an acute exercise bout, but that the response may be dependent on fitness level. A similar upregulation of circulating Klotho is also observed in response to an acute exercise in young and old mice, suggesting that this may be a good model for mechanistically probing the role of physical activity on Klotho expression. Finally, we highlight overlapping signaling pathways that are modulated by both Klotho and skeletal muscle and propose potential mechanisms for cross-talk between the two. It is hoped that this review will stimulate further consideration of the relationship between skeletal muscle activity and Klotho expression, potentially leading to important insights into the well-documented systemic anti-aging effects of exercise.
    Frontiers in Physiology 06/2014; 5:189. DOI:10.3389/fphys.2014.00189 · 3.53 Impact Factor
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