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Masaki Takasugi 《Aging cell》2018,17(2)
Cellular senescence is a cellular program that prevents the proliferation of cells at risk of neoplastic transformation. On the other hand, age‐related accumulation of senescent cells promotes aging at least partially due to the senescence‐associated secretory phenotype, whereby cells secrete high levels of inflammatory cytokines, chemokines, and matrix metalloproteinases. Emerging evidence, however, indicates that extracellular vesicles (EVs) are important mediators of the effects of senescent cells on their microenvironment. Senescent cells secrete more EphA2 and DNA via EVs, which can promote cancer cell proliferation and inflammation, respectively. Extracellular vesicles secreted from DNA‐damaged cells can also affect telomere regulation. Furthermore, it has now become clear that EVs actually play important roles in many aspects of aging. This review is intended to summarize these recent progresses, with emphasis on relationships between cellular senescence and EVs. 相似文献
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Mounolou JC Lacroute F 《Biology of the cell / under the auspices of the European Cell Biology Organization》2005,97(9):743-748
Between 1950 and 1960 mitochondria were recognized as well‐characterized organelles of animal and fungal cells. They shared more functional autonomy than other cellular structures. The transmission of some mitochondrial characteristics did not obey Mendelian rules and followed cytoplasmic inheritance patterns. Was this situation a consequence of still unknown complexities? We present a personal account on how approaches were set up to test very different hypotheses. In the end, it was shown that mitochondria had their own DNA, mitochondrial DNA, and that this molecule carried information specific to these organelles. 相似文献
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《Molecular cell》2021,81(23):4907-4923.e8
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The DNA damage response (DDR) arrests cell cycle progression until DNA lesions, like DNA double‐strand breaks (DSBs), are repaired. The presence of DSBs in cells is usually detected by indirect techniques that rely on the accumulation of proteins at DSBs, as part of the DDR. Such detection may be biased, as some factors and their modifications may not reflect physical DNA damage. The dependency on DDR markers of DSB detection tools has left questions unanswered. In particular, it is known that senescent cells display persistent DDR foci, that we and others have proposed to be persistent DSBs, resistant to endogenous DNA repair activities. Others have proposed that these peculiar DDR foci might not be sites of damaged DNA per se but instead stable chromatin modifications, termed DNA‐SCARS. Here, we developed a method, named ‘DNA damage in situ ligation followed by proximity ligation assay’ (DI‐PLA) for the detection and imaging of DSBs in cells. DI‐PLA is based on the capture of free DNA ends in fixed cells in situ, by ligation to biotinylated double‐stranded DNA oligonucleotides, which are next recognized by antibiotin anti‐bodies. Detection is enhanced by PLA with a partner DDR marker at the DSB. We validated DI‐PLA by demonstrating its ability to detect DSBs induced by various genotoxic insults in cultured cells and tissues. Most importantly, by DI‐PLA, we demonstrated that both senescent cells in culture and tissues from aged mammals retain true unrepaired DSBs associated with DDR markers. 相似文献
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细胞质雄性不育是小麦杂种优势利用的重要途径,为了鉴定3例小麦雄性不育系的细胞质类型,对其线粒体DNA(mtDNA)进行扩增片段长度多态性(Amplified fragment length polymorphism,AFLP)分析。文中利用差速离心法和不连续蔗糖密度梯度超速离心法提取纯化小麦线粒体。结果表明:通过该提取方法获得的mtDNA,其质量和纯度能够满足PCR反应和遗传学分析。在64对选扩引物中,筛选到了4对特异性引物,其中引物E1/M7在ms(Kots)-90-110不育系扩增出3条特异条带;引物E4/M2在ms(Ven)-90-110不育系扩增出2条特异条带;引物E7/M6在ms(S)-90-110不育系中扩增出2条特异条带;引物E6/M4在ms(Kots)-90-110不育系中扩增出2条特异条带。这些特异引物可以用来作为鉴定具有粘果山羊草Aegilops kotschyi、偏凸山羊草Ae.ventricosa、斯卑尔脱小麦Triticum spelta 3类不育细胞质型小麦雄性不育系的细胞质分子标记,为研究小麦细胞质雄性不育机理奠定了分子基础。 相似文献
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Mitochondrial DNA (mtDNA) is essential for the ability of mammalian cells to generate a functional oxidative phosphorylation system. Mutations in mtDNA occur in human disease and also during ageing. Here, we address three questions concerning the occurrence and accumulation of mtDNA mutations during the lifespan of the mammalian cell. What sort of mutations accumulate with age in humans and other mammals? How is the female germ line spared from the accumulation of such mutations as occurs in many somatic tissues, so that neonates normally start life with a ‘clean sheet'? Is the occurrence of mtDNA mutations associated with the functional decline of cells and tissues during ageing? We argue that mtDNA mutations in somatic cells do not just reflect a passive imprint of ageing, but they are causally associated with the loss of bioenergetic function during the ageing process. 相似文献
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自由基是一类氧化剂,对生物具有多种损害作用.衰老的自由基学说是有关衰老机理的诸多学说之一.线粒体DNA组成结构特殊,易受自由基攻击;目前认为,线粒体DNA的氧化损伤是自由基引起衰老的分子基础. 相似文献
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《Cell cycle (Georgetown, Tex.)》2013,12(21):3926-3931
Growth-promoting and nutrient/mitogen-sensing pathways such as mTOR convert p21- and p16-induced arrest into senescence (geroconversion). We have recently demonstrated that hypoxia, especially near-anoxia, suppresses geroconversion. This gerosuppressive effect of hypoxia correlated with inhibition of the mTOR/S6K pathway but not with modulation of the LKB1/AMPK/eEF2 pathway. Here we further show that mTOR inhibition is required for gerosuppression by hypoxia, at least in some cellular models, because depletion of TSC2 abolished mTOR inhibition and gerosupression by hypoxia. Also, in two cancer cell lines resistant to inhibition of mTOR by both p53 and hypoxia, hypoxia did not suppress geroconversion. Therefore, the effects of hypoxia on the oxygen-sensing mTOR pathway and geroconversion are cell type-specific. We also briefly discuss replicative senescence, organismal aging and free radical theory. 相似文献
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对水稻BT型和WA型细胞质的雄性不育系,相应保持系和恢复系以及杂种的mtDNA用12个线粒体探针进行了RFLP分析,结果如下(1)BT型和WA型不育系的mtDNA在组织结构上存在差异;(2)不育系的mtDNA与其保持系间存在显著差异,推测mtDNA与水稻的cms有关;(3)atp9探针检测到WA型不育系与F1之间的多态性,Frag36探针检测到BT型不育系与F1之间的多态性,Frag9探针检测到WA型和BT型不育系与其F1之间的多态性,证明核恢复基因影响mtDNA的结构;(4)对mtDNA的结构变异与细胞质雄性不育的关系进行了分析与探讨. 相似文献
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Mitochondrial DNA (mtDNA) of the isogamous brown alga Scytosiphon lomentaria (Lyngb.) Link is inherited maternally. We used molecular biological and morphological analyses to investigate the fate of male mitochondria. Ultrastructural observations showed that the number of 25 mitochondria in a zygote coincided with the number of mitochondria derived from male and female gametes. This number remained almost constant during the first cell division. Strain‐specific PCR in single germlings suggested that mtDNA derived from the female gamete remained in the germling during development, while the male mtDNA gradually and selectively disappeared after the four‐cell stage. One week after fertilization, male mtDNA had disappeared in sporophytic cells. Using bisulfite DNA modification and methylation mapping assays, we found that the degree of methylation on three analyzed sites of mtDNA was not different between male and female gametes, suggesting that maternal inheritance of mtDNA is not defined by its methylation. This study indicates that the mechanism of selective elimination of male mtDNA is present in each cell of a four‐celled sporophyte and that it does not depend on different degrees of DNA methylation between male and female mtDNA. 相似文献
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Growth-promoting and nutrient/mitogen-sensing pathways such as mTOR convert p21- and p16-induced arrest into senescence (geroconversion). We have recently demonstrated that hypoxia, especially near-anoxia, suppresses geroconversion. This gerosuppressive effect of hypoxia correlated with inhibition of the mTOR/S6K pathway but not with modulation of the LKB1/AMPK/eEF2 pathway. Here we further show that mTOR inhibition is required for gerosuppression by hypoxia, at least in some cellular models, because depletion of TSC2 abolished mTOR inhibition and gerosupression by hypoxia. Also, in two cancer cell lines resistant to inhibition of mTOR by both p53 and hypoxia, hypoxia did not suppress geroconversion. Therefore, the effects of hypoxia on the oxygen-sensing mTOR pathway and geroconversion are cell type-specific. We also briefly discuss replicative senescence, organismal aging and free radical theory. 相似文献
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Mitochondrial DNA (mtDNA) was isolated from over 100 different maize nucleo-cytoplasmic combinations. DNA preparations were
assayed for the presence of the 1.94kb mitochondrial plasmid by agarose gel electrophoresis and hybridization to a recombinant
clone of the plasmid. The plasmid was present in all tested inbreds which carried N, male fertile, cytoplasm or the cytoplasmically
male sterile (cms) groups,cms-T andcms-C. However, members of thecms-S group differed with respect to the presence of the plasmid. Cytoplasms I, J and S possessed the plasmid, whereas cytoplasms
B, CA, D, G, H, IA, ME, ML, PS, RD and VG did not.Cms-S group lines which had spontaneously reverted to fertility (nuclear and cytoplasmic revertants) did not exhibit a concomitant
change in 1.94kb plasmid levels, although all such lines showed the previously reported alteration in levels of the linear
mtDNAs, S1 and S2. The presence or absence of the plasmid was not correlated with (i) frequency of reversion to fertility,
(ii) the degree of male sterility expressed, (iii) the presence or absence of standard nuclear restorer to fertility genes
and (iv) nuclear genotype. Latin American races carrying RU cytoplasm possessed the plasmid, as did sweet corn varieties.
The relevance of the data tocms and evolution of thecms-S group is discussed. 相似文献
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Sheahan MB McCurdy DW Rose RJ 《The Plant journal : for cell and molecular biology》2005,44(5):744-755
Mitochondrial fusion in plants and its role in development are poorly understood. Cultured tobacco mesophyll protoplasts provide an excellent experimental system for visualizing mitochondrial dynamics. Before protoplasts first divide, mitochondria undergo a phase of extensive elongation before fission causes an increase in number, followed by actin filament (AF)-dependent dispersion that distributes mitochondria uniformly throughout the cytoplasm. Here, by fusing protoplasts containing either green fluorescent protein- or MitoTracker-labelled mitochondria, we show that elongation results from fusion during early (4-8 h) protoplast culture. This massive mitochondrial fusion (MMF) leads to near-complete mixing of the mitochondrial population within 24 h. Staining isolated mitochondria with 4',6-diamidino-2-phenylindole (DAPI) revealed that in freshly prepared protoplasts mitochondrial nucleoids were unequally distributed, with many mitochondria failing to stain with DAPI, suggesting the presence of an incomplete mitochondrial genome. Following MMF, nucleoids were distributed evenly throughout the population, thereby ensuring continuity of the mitochondrial genome in daughter cells. Massive mitochondrial fusion appears to be specific to dedifferentiation, since it also occurs in mesophyll protoplasts of Arabidopsis and Medicago but not in protoplasts from already dedifferentiated cells such as BY-2 or callus cultures. Efficient MMF requires an inner membrane electrical gradient, cytoplasmic protein synthesis, microtubules and functional kinesin but not ATP or AFs, indicating fundamental differences from mitochondrial fusion in non-plant systems. Our studies reveal that individual mitochondria are connected over time by fusion events, a finding that allows a clearer interpretation of how novel mitochondrial genotypes develop following cell fusion, and indicates that developmentally regulated fusion ensures continuity of the mitochondrial genome. 相似文献
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Bénédicte Gagny Michèle Rossignol Philippe Silar 《Fungal genetics and biology : FG & B》1997,22(3):191-198
We have cloned and sequenced the gene encoding the translation elongation factor eEF1A from two filamentous fungi,Podospora curvicollaandSordaria macrospora.These fungi are close relatives ofPodospora anserinaand also show senescence syndromes. Comparison of the sequences of the deduced proteins with that ofP. anserinareveals that the three proteins differ in several positions. Replacement of theP. anserinagene by either of the two exogenous genes does not entail any modification inP. anserinaphysiology; the longevity of the fungus is not affected. No alteration ofin vivotranslational accuracy was detected; however, the exogenous proteins nonetheless promoted a modification of the resistance to the aminoglycoside antibiotic paromomycin. These data suggest that optimization of life span between these closely related fungi has likely not been performed during evolution through modifications of eEF1A activity, despite the fact that mutations in this factor can drastically affect longevity. 相似文献