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101.
The replicative lifespan of normal somatic cells is restricted by the erosion of telomeres, which are protective caps at the
ends of linear chromosomes. The loss of telomeres induces antiproliferative signals that eventually lead to cellular senescence.
The enzyme complex telomerase can maintain telomeres, but its expression is confined to highly proliferative cells such as
stem cells and tumor cells. The immense regenerative capacity of the hematopoietic system is provided by a distinct type of
adult stem cell: hematopoietic stem cells (HSCs). Although blood cells have to be produced continuously throughout life, the
HSC pool seems not to be spared by aging processes. Indeed, limited expression of telomerase is not sufficient to prevent
telomere shortening in these cells, which is thought ultimately to limit their proliferative capacity. In this review, we
discuss the relevance of telomere maintenance for the hematopoietic stem cell compartment and consider potential functions
of telomerase in this context. We also present possible clinical applications of telomere manipulation in HSCs and new insights
affecting the aging of the hematopoietic stem cell pool and replicative exhaustion.
This work was supported by European Community Grant LSHC-CT-2004-502943 (MOL CANCER MED). 相似文献
102.
豌豆根瘤侵染细胞衰老过程的电镜观察 总被引:5,自引:0,他引:5
用透射电镜观察了豌豆根瘤侵染细胞在衰老过程中的超微结构变化,结果表明,侵染细胞和拟菌体的衰老有一定的规律和特征,首先是一些包裹拟菌体的包囊变得疏松,包囊和拟菌体之间出现较大间隙,间隙中常有一些纤维状和泡状物质。然后,细胞质失去正常结构,逐渐凝聚为染色很深的团块,进而完全泡状化,伴随着拟菌体的衰老,寄主细胞质染色由深变浅,细胞器逐渐减少,最后,液泡和质膜相继破裂,细胞完全瓦解,有时在衰老细胞的胞间隙,或在衰老的细胞质中有一定年轻的细菌,甚至在一片崩溃的拟菌体中还有侵染丝,有的还正在向寄主细胞质释放细菌。 相似文献
103.
胡萝卜素产生菌三孢布拉霉(Blakeslea trispora)的老化现象及其特征。其老化菌株通过菌丝接触,将老化性状传递给正常菌株。并通过转变正常菌株的孢予,使老化性状传递给后代。菌丝的老化伴随着体内胡萝卜素的消失。 相似文献
104.
105.
Makoto Matsuyama Hiroki Tanaka Akihito Inoko Hidemasa Goto Shigenobu Yonemura Kyoko Kobori Yuko Hayashi Eisaku Kondo Shigeyoshi Itohara Ichiro Izawa Masaki Inagaki 《The Journal of biological chemistry》2013,288(50):35626-35635
Vimentin, a type III intermediate filament (IF) protein, is phosphorylated predominantly in mitosis. The expression of a phosphorylation-compromised vimentin mutant in T24 cultured cells leads to cytokinetic failure, resulting in binucleation (multinucleation). The physiological significance of intermediate filament phosphorylation during mitosis for organogenesis and tissue homeostasis was uncertain. Here, we generated knock-in mice expressing vimentin that have had the serine sites phosphorylated during mitosis substituted by alanine residues. Homozygotic mice (VIMSA/SA) presented with microophthalmia and cataracts in the lens, whereas heterozygotic mice (VIMWT/SA) were indistinguishable from WT (VIMWT/WT) mice. In VIMSA/SA mice, lens epithelial cell number was not only reduced but the cells also exhibited chromosomal instability, including binucleation and aneuploidy. Electron microscopy revealed fiber membranes that were disorganized in the lenses of VIMSA/SA, reminiscent of similar characteristic changes seen in age-related cataracts. Because the mRNA level of the senescence (aging)-related gene was significantly elevated in samples from VIMSA/SA, the lens phenotype suggests a possible causal relationship between chromosomal instability and premature aging. 相似文献
106.
107.
Bethan Britt-Compton 《FEBS letters》2009,583(18):3076-89
Short telomeres have been shown to be preferentially elongated in both yeast and mouse models. We examined this in human cells, by utilising cells with large allelic telomere length differentials and observing the relative rates of elongation following the expression of hTERT. We observed that short telomeres are gradually elongated in the first 26 PDs of growth, whereas the longer telomeres displayed limited elongation in this period. Telomeres coalesced at similar lengths irrespective of their length prior to the expression of hTERT. These data indicate that short telomeres are marked for gradual elongation to a cell strain specific length threshold. 相似文献
108.
Selenium unmasks protective iron armor: A possible defense against cutaneous inflammation and cancer
Jack L. Arbiser Michael Y. Bonner Nicole Ward Justin Elsey Shikha Rao 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(11):2518-2527
Background
A link between selenium deficiency and inflammatory skin diseases have been noted by many, but this link is still not well understood. We have previously studied the efficacy of ceramide analogs, based on the fire ant venom Solenopsin A, against our psoriasis animal model. Treatment of animals with solenopsin analogs resulted in significantly improved skin as well as in a coordinate downregulation of selenoproteins, namely Glutathione Peroxidase 4 (GPX4). We thus hypothesize that ferroptosis may be a physiologic process that may protect the skin from both inflammatory and neoplastic processes.Methods
We analyze and compare gene expression profiles in the GEO database from clinical skin samples taken from healthy patients and psoriasis patients (both involved and noninvolved skin lesions). We validated the gene expression results against a second, independent, cohort from the GEO database.Results
Significant reduction in gene expression of GPX4, elevated expression of Nrf2 downstream targets, and expression profiles mirroring erastin-inhibition of Cystine/Glutamate Antiporter-System XC activity in psoriatic skin lesions, compared to both noninvolved skin and healthy patient samples, suggest an innately inducible mechanism of ferroptosis.Conclusions
We present data that may indicate selenoproteins, particularly GPX4, in resolving inflammation and skin cancer, including the novel hypothesis that the human organism may downregulate GPX4 and reactive oxygen (REDOX) regulating proteins in the skin as a way of resolving psoriasis and nonmelanoma skin cancer through increased reactive oxygen species. Further studies are needed to investigate ferroptosis as a possible physiologic mechanism for eliminating inflammatory and malignant tissues.General significance
This study provides a fresh framework for understanding the seemingly contradictory effects of selenium supplementation. In addition, it offers a novel explanation of how physiologic upregulation of ferroptosis and downregulation of selenoprotein synthesis may mediate resolution of inflammation and carcinogenesis. This is of therapeutic significance. 相似文献109.
Katia Fettucciari Lara Macchioni Magdalena Davidescu Paolo Scarpelli Camilla Palumbo Lanfranco Corazzi Andrea Marchegiani Matteo Cerquetella Andrea Spaterna Pierfrancesco Marconi Gabrio Bassotti 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2018,1865(12):1945-1958
Clostridium difficile infection (CDI) causes nosocomial/antibiotic-associated diarrhea and pseudomembranous colitis, with dramatic incidence/mortality worldwide. C. difficile virulence factors are toxin A and toxin B (TcdB) which cause cytopathic/cytotoxic effects and inflammation. Until now studies were focused on molecular effects of C. difficile toxins (Tcds) on different cells while unexplored aspect is the status/fate of cells that survived their cytotoxicity. Recently we demonstrated that enteric glial cells (EGCs) are susceptible to TcdB cytotoxicity, but several EGCs survived and were irreversibly cell-cycle arrested and metabolically active, suggesting that EGCs could became senescent. This is important because allowed us to evaluate the not explored status/fate of cells surviving Tcds cytotoxicity, and particularly if TcdB induces senescence in EGCs.Rat-transformed EGCs were treated with 10?ng/ml TcdB for 6?h–48?h, or for 48?h, followed by incubation for additional 4 or 11?days in absence of TcdB (6 or 13 total days). Senescence markers/effectors were examined by specific assays.TcdB induces senescence in EGCs, as demonstrated by the senescence markers: irreversible cell-cycle arrest, senescence-associated-β?galactosidase positivity, flat morphology, early and persistent DNA damage (ATM and H2AX phosphorylation), p27 overexpression, pRB hypophosphorylation, c?Myc, cyclin B1, cdc2 and phosphorylated-cdc2 downregulation, Sirtuin?2 and Sirtuin?3 overexpression. TcdB-induced EGC senescence is dependent by JNK and AKT activation but independent by ROS, p16 and p53/p21 pathways.In conclusion, TcdB induces senescence in EGCs. The extrapolation of these results to CDI leads to hypothesize that EGCs that survived TcdB, once they have acquired a senescence state, could cause irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and tumors due to persistent inflammation, transfer of senescence status and stimulation of pre-neoplastic cells. 相似文献
110.