Telomere shortening as a hallmark of stem cell senescence

Fathi, Ezzatollah; Charoudeh, Hojjatollah Nozad; Sanaat, Zohreh; Farahzadi, Raheleh

doi:10.21037/sci.2019.02.04

Cited by 57 publications

(38 citation statements)

References 38 publications

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“…These factors regulate BMSCs either to proliferate, die, or undergo a permanent cell cycle arrest [30]. Factors that lead the BMSCs and other cells to senescence include telomeres shortening, genotoxic stresses/DNA damage, strong mitogenic signals, oxidative stress, and distortions in chromatin organization [29,[31][32][33]. Actually, all of these factors have the ability to elicit a DNA damage response (DDR).…”

Section: Senescence Of Bmscs and Senile Osteoporosismentioning

confidence: 99%

Senile Osteoporosis: The Involvement of Differentiation and Senescence of Bone Marrow Stromal Cells

Qadir

Liang

et al. 2020

IJMS

156

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Senile osteoporosis has become a worldwide bone disease with the aging of the world population. It increases the risk of bone fracture and seriously affects human health. Unlike postmenopausal osteoporosis which is linked to menopause in women, senile osteoporosis is due to aging, hence, affecting both men and women. It is commonly found in people with more than their 70s. Evidence has shown that with age increase, bone marrow stromal cells (BMSCs) differentiate into more adipocytes rather than osteoblasts and undergo senescence, which leads to decreased bone formation and contributes to senile osteoporosis. Therefore, it is necessary to uncover the molecular mechanisms underlying the functional changes of BMSCs. It will benefit not only for understanding the senile osteoporosis development, but also for finding new therapies to treat senile osteoporosis. Here, we review the recent advances of the functional alterations of BMSCs and the related mechanisms during senile osteoporosis development. Moreover, the treatment of senile osteoporosis by aiming at BMSCs is introduced.

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Section: Senescence Of Bmscs and Senile Osteoporosismentioning

confidence: 99%

Senile Osteoporosis: The Involvement of Differentiation and Senescence of Bone Marrow Stromal Cells

Qadir

Liang

et al. 2020

IJMS

156

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“…Besides having a unique DNA sequence, the protection of chromosomes depends on the association and interaction of human telomeres with the shelterin complex, which contains six specific proteins (TRF1, TRF2, POT1, TIN2, TPP1, and RAP1). This network provides a compact chromatin structure that limits the accessibility of DNA damage repair (DDR) machinery and decreases its mistaken recognition at the telomere region ( Bandaria et al, 2016 ; Fathi et al, 2019 ) ( Figure 1A ). Since DNA polymerase is unable to fully replicate the 3' end of the DNA strand, telomeres lose part of its sequence with each cell division and reach a critical short length, which, in turn, leads to cellular senescence ( Stewart et al, 2003 ).…”

Section: Telomeres: Structure and Functionsmentioning

confidence: 99%

Telomere-Related Disorders in Fetal Membranes Associated With Birth and Adverse Pregnancy Outcomes

Polettini

Silva

2020

Front. Physiol.

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Telomere disorders have been associated with aging-related diseases, including diabetes, vascular, and neurodegenerative diseases. The main consequence of altered telomere is the induction of the state of irreversible cell cycle arrest. Though several mechanisms responsible for the activation of senescence have been identified, it is still unclear how a cell is indeed induced to become irreversibly arrested. Most tissues in the body will experience senescence throughout its lifespan, but intrinsic and extrinsic stressors, such as chemicals, pollution, oxidative stress (OS), and inflammation accelerate the process. Pregnancy is a state of OS, as the higher metabolic demand of the growing fetus results in increased reactive oxygen species production. As a temporary organ in the mother, senescence in fetal membranes and placenta is expected and linked to term parturition (>37 weeks of gestation). However, a persistent, overwhelming, or premature OS affects placental antioxidant capacity, with consequent accumulation of OS causing damage to lipids, proteins, and DNA in the placental tissues. Therefore, senescence and its main inducer, telomere length (TL) reduction, have been associated with pregnancy complications, including stillbirth, preeclampsia, intrauterine growth restriction, and prematurity. Fetal membranes have a notable role in preterm births, which continue to be a major health issue associated with increased risk of neo and perinatal adverse outcomes and/or predisposition to disease in later life; however, the ability to mediate a delay in parturition during such cases is limited, because the pathophysiology of preterm births and physiological mechanisms of term births are not yet fully elucidated. Here, we review the current knowledge regarding the regulation of telomere-related senescence mechanisms in fetal membranes, highlighting the role of inflammation, methylation, and telomerase activity. Moreover, we present the evidences of TL reduction and senescence in gestational tissues by the time of term parturition. In conclusion, we verified that telomere regulation in fetal membranes requires a more complete understanding, in order to support the development of successful effective interventions of the molecular mechanisms that triggers parturition, including telomere signals, which may vary throughout placental tissues.

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“…Notably, short telomeres affect the proliferation, self-renewal, and commitment of progenitor cells [28] and induce alterations during their differentiation process in embryonic stem cells [16]. However, while telomere length is important to counteract mesenchymal stem cell senescence, [29], telomerase activity plays an important role in the differentiation process [30]. Increased telomerase activity due to the overexpression of human telomerase reverse transcriptase (hTERT) gene in hMSCs promotes osteoblast differentiation in vitro as well as heterotopic bone formation in vivo [31, 32].…”

Section: Introductionmentioning

confidence: 99%

Increased Gene Expression of RUNX2 and SOX9 in Mesenchymal Circulating Progenitors Is Associated with Autophagy during Physical Activity

Carbonare

Mottes

Cheri

et al. 2019

Oxidative Medicine and Cellular Longevity

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Lack of physical exercise is considered an important risk factor for chronic diseases. On the contrary, physical exercise reduces the morbidity rates of obesity, diabetes, bone disease, and hypertension. In order to gain novel molecular and cellular clues, we analyzed the effects of physical exercise on differentiation of mesenchymal circulating progenitor cells (M-CPCs) obtained from runners. We also investigated autophagy and telomerase-related gene expression to evaluate the involvement of specific cellular functions in the differentiation process. We performed cellular and molecular analyses in M-CPCs, obtained by a depletion method, of 22 subjects before (PRE RUN) and after (POST RUN) a half marathon performance. In order to prove our findings, we performed also in vitro analyses by testing the effects of runners' sera on a human bone marrow-derived mesenchymal stem (hBM-MSC) cell line. PCR array analyses of PRE RUN versus POST RUN M-CPC total RNAs put in evidence several genes which appeared to be modulated by physical activity. Our results showed that physical exercise promotes differentiation. Osteogenesis-related genes as RUNX2, MSX1, and SPP1 appeared to be upregulated after the run; data showed also increased levels of BMP2 and BMP6 expressions. SOX9, COL2A1, and COMP gene enhanced expression suggested the induction of chondrocytic differentiation as well. The expression of telomerase-associated genes and of two autophagy-related genes, ATG3 and ULK1, was also affected and correlated positively with MSC differentiation. These data highlight an attractive cellular scenario, outlining the role of autophagic response to physical exercise and suggesting new insights into the benefits of physical exercise in counteracting chronic degenerative conditions.

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Telomere shortening as a hallmark of stem cell senescence

Cited by 57 publications

References 38 publications

Senile Osteoporosis: The Involvement of Differentiation and Senescence of Bone Marrow Stromal Cells

Senile Osteoporosis: The Involvement of Differentiation and Senescence of Bone Marrow Stromal Cells

Telomere-Related Disorders in Fetal Membranes Associated With Birth and Adverse Pregnancy Outcomes

Increased Gene Expression of RUNX2 and SOX9 in Mesenchymal Circulating Progenitors Is Associated with Autophagy during Physical Activity

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