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《生物化学与生物物理进展》2018,(9)
衰老是一种在细胞和组织水平逐渐发生功能衰退的过程.早衰症是一类罕见的人类遗传性疾病,以加速衰老为特征.对早衰症的研究有助于理解人类衰老的生理过程,对衰老相关疾病的防治具有借鉴意义.成人早衰症和儿童早衰症是两种著名的人类早衰症,本文将综述这两种早衰症的发病机制及干预方法. 相似文献
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阿尔茨海默病（Alzheimers’ disease, AD）是一种常见的以进行性认知障碍和记忆减退为主要特征的中枢神经退行性疾病,发病人数多,波及范围广,已成为老年医学中最严峻的问题之一。临床上AD的药物治疗效果有限,且存在一定的局限性与副作用。目前,物理干预AD的治疗方法正逐渐受到人们的关注和重视,研究表明,物理干预如嗅觉干预、光疗法、脑电刺激、声光刺激、温度干预等能通过提高神经发生、神经保护、调控神经元兴奋性和可塑性、提高脑血流量、改善代谢、减少Aβ沉积和Tau蛋白过度磷酸化等,从而改善AD症状与认知功能。本文综述了不同物理干预对AD的作用机制以及疗效,为物理干预用于实施预防和延缓AD提供理论基础。 相似文献
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物质使用障碍（substance use disorder,SUD）是一个全球性的卫生和社会问题。针对大多数成瘾性物质,目前还没有有效的治疗药物,普遍还是采用心理治疗和行为矫治。近年来,针刺、深部脑刺激（DBS）、重复经颅磁刺激（rTMS）、经颅直流电刺激（tDCS）和运动等非药物干预手段在治疗神经系统疾病的有效性逐渐得到重视。越来越多的研究也开始关注非药物干预手段在治疗SUD中的应用。本综述在文献检索（如PubMed、Google Scholar等）的基础上总结了针刺、DBS、rTMS、tDCS和运动等非药物干预手段对阿片类药物、精神活性物质、尼古丁、酒精等不同成瘾性物质的心理渴求、戒断时间、使用剂量和成瘾伴随的情绪、认知功能障碍等的影响。研究表明,针刺、DBS、rTMS、tDCS和运动等非药物干预手段可以有效降低成瘾性物质引起的心理渴求、降低物质摄入量、增加戒断时间,同时改善长期使用成瘾性物质引起的认知障碍、焦虑和抑郁样行为等。如果非药物干预手段结合药物、心理等治疗方式,效果更佳。尽管非药物干预方法在现阶段主要作为辅助性治疗手段,未来的研究应注重明确非药物干预手段的神经生物学机制,... 相似文献
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肝纤维化(liver fibrosis,LF)是一种可由多种致病因素导致的疾病,由于尚无有效的治疗手段,其已经严重地威胁着全球人的健康。虽然LF可以逆转,但更多会发生恶化进而发展为肝硬化和肝癌。目前为止,其发病机制已经可以从多方面被阐述。肝星状细胞(hepatic stellate cells,HSCs)是LF发展的中心和关键,而其他细胞也成为影响纤维化必不可少的因素。它们以细胞因子为联系,并大量分泌首要的细胞因子-转化生长因子-β1-来刺激HSCs的激活和增殖。最终,它们共同导致胶原的沉积和细胞外基质(extracellular matrix,ECM)结构的紊乱。而这其中,长链非编码RNA也积极参与了对纤维化过程的影响。本综述将从细胞、细胞因子、ECM以及基因等方面对LF的发生和发展进行探讨,从而有助于我们明确LF的发病机制,并为研发LF有效的治疗方法提供方向。 相似文献
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阿尔茨海默病(Alzheimer's disease,AD)是一种慢性进行性神经变性疾病,早期临床表现为近期记忆力下降,后来逐渐发展为生活不能自理最终死亡。目前,有许多种假说阐述其发病机制,如β-淀粉样蛋白、载脂蛋白E、一些金属元素、炎症因子等,但都不全面,也有人认为其可能与朊蛋白有关。部分药物被用于治疗AD,如美金刚、胆碱酯酶抑制剂等,但疗效均不显著。一些新的治疗理念和方法也逐渐被发现,如脑源性神经生长因子(brain-derived neurotrophic factor,BDNF)以及免疫疗法等,但其远期疗效还需进一步证实,且一些副作用还并未被人们所知晓。本文主要对阿尔茨海默病的发病机制及药物治疗的研究进展进行了综述。 相似文献
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肿瘤干细胞具有自我更新和可塑性的潜能,能够维持肿瘤生长和异质性的能力．肿瘤干细胞是肿瘤产生、转移、耐药和复发的根源,肿瘤干细胞学说逐渐被肿瘤研究者所接受,因此,对肿瘤干细胞的深入理解有重大的科学和临床意义．肿瘤干细胞的微环境是肿瘤微环境的组成部分,包括细胞-细胞接触、分泌型因子等．肿瘤非干细胞和肿瘤干细胞本身都可以作为肿瘤干细胞的微环境．肿瘤干细胞的微环境可以维持肿瘤干细胞的可塑性,保护肿瘤干细胞免受免疫系统攻击,也可以促进其转移．肿瘤干细胞对其微环境的塑造、肿瘤干细胞的微环境对肿瘤干细胞自我更新的影响,以及针对肿瘤干细胞微环境的靶向干预等问题,已成为肿瘤干细胞研究的前沿问题．本文就肿瘤干细胞的发现、自我更新维持机制、肿瘤干细胞的微环境,及其肿瘤干细胞及微环境的干预策略等研究进展进行了综述． 相似文献
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强迫症是以具有反复强迫思维和强迫行为为特征的一种心理障碍疾病。该病严重影响人们的心理健康和日常生活,因而受到广泛的关注。强迫症病因比较复杂,受到多种因素的影响,家庭环境、社会氛围、个人受教育程度、智力水平及个体的身体素质、健康状况及个性特点等因素与强迫症的产生密切相关。对强迫症的生物学机制的研究主要集中在对相关基因的研究上,其中五羟色胺和多巴胺在强迫症中的作用机制相对来说研究的比较多,也比较成熟,近年来又发现谷氨酸通路和白细胞介素-10也与强迫症的发生有关。与此同时一些治疗强迫症的方法也涌现了出来,如药物治疗和心理治疗。本文拟从强迫症的概念、临床表现、影响因素、生物学机制及其治疗方法等方面的研究进行阐述,以期为今后的研究提供一些参考和依据。 相似文献
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可逆性后部脑病综合征是一种与多种致病因素相关的临床影像学综合征,以头痛、癫痫发作、精神症状、视觉障碍、意识障碍为主要临床表现,影像学以顶枕叶可逆性脑白质病变为主。该病如果能够得到及时的诊断与治疗,大部分患者的临床症状及影像学改变可以消失;如果不能得到及时正确的诊疗,可能会发生一些不可逆的损伤,严重时甚至危及生命,因此加强对本病的认识、诊断及治疗至关重要。目前该病的发病机制尚不明确,现对其发病机制进展及影像学表现进行综述,以提高临床医师对该病的病理生理机制的认识及提高诊断水平。 相似文献
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血管老化是一个古老而又年轻的课题.本文综述了血管衰老的主要结构特征、功能改变及其机制的新近研究进展,重点就血管基质变化、内皮细胞衰老/功能失调、内皮祖细胞衰竭以及细胞间通讯等方面进行了阐述. 相似文献
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应激性心肌病(SCM)属于临床上较为常见的一种急性心血管病事件,其中心理因素、疾病因素、药物因素以及躯体应激因素等均可诱发该病。SCM患者的主要表现为胸痛,且伴有可逆性左心室功能障碍、心肌损伤标志物水平异常以及心电图异常等,与急性心肌梗死存在高度相似。SCM患者心室造影可见左室心尖部收缩力明显下降,心底部代偿性收缩增强,从而导致患者左室于收缩末期主要形态为圆底窄颈。由于SCM患者的收缩期左室造影形状和日本渔民用以捕捉章鱼的鱼篓相似,因此SCM又被称之为章鱼篓心肌病。本研究主要是通过患者的临床表现、诊断以及发病机制三个方面对SCM的研究进展进行综述,旨在为临床SCM的防治提供参考依据。 相似文献
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Zeming Wu Weiqi Zhang Moshi Song Wei Wang Gang Wei Wei Li Jinghui Lei Yu Huang Yanmei Sang Piu Chan Chang Chen Jing Jing Keiichiro Suzuki Juan Carlos Izpisua Belmonte Guang-Hui Liu 《蛋白质与细胞》2018,9(4):333
Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome (WS) are two of the best characterized human progeroid syndromes. HGPS is caused by a point mutation in lamin A (LMNA) gene, resulting in the production of a truncated protein product—progerin. WS is caused by mutations in WRN gene, encoding a loss-of-function RecQ DNA helicase. Here, by gene editing we created isogenic human embryonic stem cells (ESCs) with heterozygous (G608G/+) or homozygous (G608G/G608G) LMNAmutation and biallelic WRN knockout, for modeling HGPS and WS pathogenesis, respectively. While ESCs and endothelial cells (ECs) did not present any features of premature senescence, HGPS- and WS-mesenchymal stem cells (MSCs) showed aging-associated phenotypes with different kinetics. WS-MSCs had early-onset mild premature aging phenotypes while HGPS-MSCs exhibited late-onset acute premature aging characterisitcs. Taken together, our study compares and contrasts the distinct pathologies underpinning the two premature aging disorders, and provides reliable stem-cell based models to identify new therapeutic strategies for pathological and physiological aging. 相似文献
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Diego Quintana-Torres Alejandra Valle-Cao Pablo Bousquets-Muñoz Sandra Freitas-Rodríguez Francisco Rodríguez Alejandro Lucia Carlos López-Otín Alejandro López-Soto Alicia R. Folgueras 《Aging cell》2023,22(10):e13952
Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disease caused by nuclear envelope alterations that lead to accelerated aging and premature death. Several studies have linked health and longevity to cell-extrinsic mechanisms, highlighting the relevance of circulating factors in the aging process as well as in age-related diseases. We performed a global plasma proteomic analysis in two preclinical progeroid models (LmnaG609G/G609G and Zmpste24−/− mice) using aptamer-based proteomic technology. Pathways related to the extracellular matrix, growth factor response and calcium ion binding were among the most enriched in the proteomic signature of progeroid samples compared to controls. Despite the global downregulation trend found in the plasma proteome of progeroid mice, several proteins associated with cardiovascular disease, the main cause of death in HGPS, were upregulated. We also developed a chronological age predictor using plasma proteome data from a cohort of healthy mice (aged 1–30 months), that reported an age acceleration when applied to progeroid mice, indicating that these mice exhibit an “old” plasma proteomic signature. Furthermore, when compared to naturally-aged mice, a great proportion of differentially expressed circulating proteins in progeroid mice were specific to premature aging, highlighting secretome-associated differences between physiological and accelerated aging. This is the first large-scale profiling of the plasma proteome in progeroid mice, which provides an extensive list of candidate circulating plasma proteins as potential biomarkers and/or therapeutic targets for further exploration and hypothesis generation in the context of both physiological and premature aging. 相似文献
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早老素（progerin）的累积导致儿童早老症（Hutchinson Gilford progeria syndrome, HGPS）的发生,并与正常衰老相关。早老素能使细胞内稳态失衡但分子机制仍有待深入研究。本研究旨在探讨早老素导入人胚胎肾293T细胞（human embryo kidney 293T cell, HEK293T）后细胞增殖、周期变化的分子机制。形态学观察发现过表达早老素的HEK293T细胞密度下降,(57±2.47)%细胞核形态皱缩。细胞增殖和周期实验证明早老素使细胞增殖减慢,发生G1/S期阻滞,G1细胞从 (42.3±1.31)%升至(47.2±1.26)%,而S期细胞从 (43.1±1.36)%降至 (38.5±1.42)%。Western印迹结果显示早老素的高表达引起p21蛋白表达上调（103.2±1.49）%,CDK4下调（63±1.52）%,而p53、ATM、CyclinE1以及p16等蛋白质水平均不变;HEK293T细胞中早老素的过表达导致γ H2AX水平下调（53±1.36）%,H2O2处理后变化趋势不变。我们的研究结果提示,早老素通过上调p21和下调CDK4使细胞发生周期阻滞,不能增加HEK293T细胞的损伤及衰老。 相似文献
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Investigating the molecular basis of aging has been difficult, primarily owing to the pleiotropic and segmental nature of the aging phenotype. There are many often interacting symptoms of aging, some of which are obvious and appear to be common to every aged individual, whereas others affect only a subset of the elderly population. Although at first sight this would suggest multiple molecular mechanisms of aging, there now appears to be almost universal consensus that aging is ultimately the result of the accumulation of somatic damage in cellular macromolecules, with reactive oxygen species likely to be the main damage-inducing agent. What remains significant is unravelling how such damage can give rise to the large variety of aging symptoms and how these can be controlled. Although humans, with over a century of clinical observations, remain the obvious target of study, the mouse, with a relatively short lifespan, easy genetic accessibility and close relatedness to humans, is the tool par excellence to model aging-related phenotypes and test strategies of intervention. Here we present the argument that mouse models with engineered defects in genome maintenance systems are especially important because they often exhibit a premature appearance of aging symptoms. Confirming studies on human segmental progeroid syndromes, most of which are based on heritable mutations in genes involved in genome maintenance, the results thus far obtained with mouse models strongly suggest that lifespan and onset of aging are directly related to the quality of DNA metabolism. This may be in keeping with the recent discovery of a possible 'universal survival' pathway that improves antioxidant defence and genome maintenance and simultaneously extends lifespan in the mouse and several invertebrate species. 相似文献
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《Biomarkers》2013,18(8):679-685
Objective: To assess differences in kidney function between Down syndrome (DS) individuals and a control group related to aging.Methods: Creatinine (Cr) and specific gravity (SG) were assessed by spectrophotometric and refractometric assays in urine samples of 103 individuals with DS and 82 age-matched controls.Results: Significantly lower levels of Cr and SG were found in DS after puberty. Significant correlations were found between SG and age as well as between Cr and SG in DS and controls (p?≤?0.05).Conclusions: Premature aging in kidneys of DS patients could lead to an impaired renal function. 相似文献
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Lamin A-dependent nuclear aberration and DNA damage was found in premature aging disease or normally old individuals. In this study, UVB irradiation was used as a cellular senescence inducer, and it was found that Lamin A and phospho-H2AX protein was increased by UVB treatment on normal human fibroblast. Lamin A-dependent morphological nuclear defect was observed in UVB treated fibroblast. Amentoflavone, a well known biflavonoid, inhibited the increase of Lamin A or phospho-H2AX protein in dose dependent manner which was induced by UVB irradiation, and also protected nuclear aberration dramatically. These results indicated that amentoflavone is an anti-aging candidate for UVB related skin aging process. 相似文献
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Young Sun Oh Dae Gyu Kim Gyuyoup Kim Eung‐Chil Choi Brian K. Kennedy Yousin Suh Bum Joon Park Sunghoon Kim 《Aging cell》2010,9(5):810-822
Although AIMP3/p18 is normally associated with the macromolecular tRNA synthetase complex, recent reports have revealed a new role of AIMP3 in tumor suppression. In this study, we generated a transgenic mouse that overexpresses AIMP3 and characterized the associated phenotype in vivo and in vitro. Surprisingly, the AIMP3 transgenic mouse exhibited a progeroid phenotype, and the cells that overexpressed AIMP3 showed accelerated senescence and defects in nuclear morphology. We found that overexpression of AIMP3 resulted in proteasome‐dependent degradation of mature lamin A, but not of lamin C, prelamin A, or progerin. The resulting imbalance in the protein levels of lamin A isoforms, namely altered stoichiometry of prelamin A and progerin to lamin A, appeared to be responsible for a phenotype that resembled progeria. An increase in the level of endogenous AIMP3 has been observed in aged human tissues and cells. The findings in this report suggest that AIMP3 is a specific regulator of mature lamin A and imply that enhanced expression of AIMP3 might be a factor driving cellular and/or organismal aging. 相似文献