When stem cells grow old: phenotypes and mechanisms of stem cell aging

Schultz, Michael; Sinclair, David A.

doi:10.1242/dev.130633

Cited by 287 publications

(277 citation statements)

References 212 publications

(256 reference statements)

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“…While telomere length decreases with an individual's age, recent data suggest that after the age of 75, it becomes positively correlated with age implying its significance for survival in the very old age. 15,22 In terms of MSC aging, this theory has been extensively tested using serially passaged MSCs, where an average 17 base pair telomere loss with each population doubling was confirmed. 21,23 The stem cell theory of aging postulates a decline in stem cell number and functionalities as a potential effect of aging.…”

Section: General Theories Of Agingmentioning

confidence: 99%

“…[24][25][26] Schultz and Sinclair have discussed that the probable causes of cellular aging (i.e., the abovementioned telomere attrition, DNA damage, and cellular senescence) can also be applied to stem cells. 15 Fukada et al have not only described the aging of stem cells but have also connected the other theories with the stem cell theory to explain the complex progression of aging. 18 As BMMSCs can be viewed as true stem cells, 27 the stem cell theory is linked to each of the theories mentioned above.…”

Section: General Theories Of Agingmentioning

confidence: 99%

See 1 more Smart Citation

Age Related Changes in Bone Marrow Mesenchymal Stromal Cells: A Potential Impact on Osteoporosis and Osteoarthritis Development

et al. 2017

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Aging at the cellular level is a complex process resulting from accumulation of various damages leading to functional impairment and a reduced quality of life at the level of the organism. With a rise in the elderly population, the worldwide incidence of osteoporosis (OP) and osteoarthritis (OA) has increased in the past few decades. A decline in the number and "fitness" of mesenchymal stromal cells (MSCs) in the bone marrow (BM) niche has been suggested as one of the factors contributing to bone abnormalities in OP and OA. It is well recognized that MSCs in vitro acquire culture-induced aging features such as gradual telomere shortening, increased numbers of senescent cells, and reduced resistance to oxidative stress as a result of serial population doublings. In contrast, there is only limited evidence that human BM-MSCs "age" similarly in vivo. This review compares the various aspects of in vitro and in vivo MSC aging and suggests how our current knowledge on rejuvenating cultured MSCs could be applied to develop future strategies to target altered bone formation processes in OP and OA.

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Section: General Theories Of Agingmentioning

confidence: 99%

Section: General Theories Of Agingmentioning

confidence: 99%

Age Related Changes in Bone Marrow Mesenchymal Stromal Cells: A Potential Impact on Osteoporosis and Osteoarthritis Development

et al. 2017

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“…It is not clear; however, if defective or reduced adult stem cell pools are responsible for the dysfunction of tissues in old organisms or, conversely, if aging causes a reduction in the number and/or functionality of the stem cells (Goodell & Rando, 2015; Schultz & Sinclair, 2016; Sharpless & DePinho, 2007). …”

Section: Introduction Results Discussionmentioning

confidence: 99%

Adult Sox2+ stem cell exhaustion in mice results in cellular senescence and premature aging

et al. 2018

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Aging is characterized by a gradual functional decline of tissues with age. Adult stem and progenitor cells are responsible for tissue maintenance, repair, and regeneration, but during aging, this population of cells is decreased or its activity is reduced, compromising tissue integrity and causing pathologies that increase vulnerability, and ultimately lead to death. The causes of stem cell exhaustion during aging are not clear, and whether a reduction in stem cell function is a cause or a consequence of aging remains unresolved. Here, we took advantage of a mouse model of induced adult Sox2+ stem cell depletion to address whether accelerated stem cell depletion can promote premature aging. After a short period of partial repetitive depletion of this adult stem cell population in mice, we observed increased kyphosis and hair graying, and reduced fat mass, all of them signs of premature aging. It is interesting that cellular senescence was identified in kidney after this partial repetitive Sox2+ cell depletion. To confirm these observations, we performed a prolonged protocol of partial repetitive depletion of Sox2+ cells, forcing regeneration from the remaining Sox2+ cells, thereby causing their exhaustion. Senescence specific staining and the analysis of the expression of genetic markers clearly corroborated that adult stem cell exhaustion can lead to cellular senescence induction and premature aging.

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“…Further up the vertical axis of the crypt at position +4, there was a second population of stem cells which were generally in a quiescent state [24] . A number of genes have been used as markers to characterize this second cell population but, as noted by Clevers [23] , these different gene markers may actually be identifying different subpopulations.…”

Section: Intestinal Stem Cells A) Heterogeneity Of Stem Cell Populationmentioning

confidence: 99%

“…The aging of intestinal stem cells has been studied most extensively in the invertebrate Drosophila [24] . In the fly, intestinal stem cells undergo asymmetric division with one of the daughter cells (enteroblast) being the progenitor of two differentiated cell types; enteroendocrine cells and enterocytes [27] .…”

Section: C) Agingmentioning

confidence: 99%

Stem cells and Aging

Singer

2016

Stem Cell Transl Investig

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The prevailing view of the aging process is that it reflects the integrated sequelae of accumulated random biological damage. These sequelae have been referred to as the hallmarks of aging and one of these hallmarks is the age-related decline in somatic stem cell functions; termed stem cell exhaustion. This stem cell exhaustion construct implies that stem cell aging across different tissues should have a number of similar characteristics. However, such is not the case. The characteristics of aging for stem cell populations in a variety of tissues, (hair follicle, skeletal muscle, hematopoietic tissue, skin, intestine and testes), display many distinctive tissue specific features. This observation implies that stem cell exhaustion is not a generic process consequent to the accumulation of random biological damage but rather represents the manifestation of tissue specific evolved programs.

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When stem cells grow old: phenotypes and mechanisms of stem cell aging

Cited by 287 publications

References 212 publications

Age Related Changes in Bone Marrow Mesenchymal Stromal Cells: A Potential Impact on Osteoporosis and Osteoarthritis Development

Age Related Changes in Bone Marrow Mesenchymal Stromal Cells: A Potential Impact on Osteoporosis and Osteoarthritis Development

Adult Sox2+ stem cell exhaustion in mice results in cellular senescence and premature aging

Stem cells and Aging

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