共查询到19条相似文献,搜索用时 141 毫秒
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细胞自噬和衰老及衰老相关疾病密切相关。从自噬角度延缓衰老和治疗衰老相关疾病的方法包括使用自噬诱导剂、抗氧化剂和热量限制。本文就自噬和衰老及衰老相关疾病的关系及机制方面做一综述,以提高临床医师的认识。 相似文献
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心血管系统维持着机体正常的生命活动,心血管系统衰老可引发高血压、动脉粥样硬化、心力衰竭、心肌梗死等疾病。自噬是一种溶酶体依赖性降解途径,其水平随着年龄增加而逐渐降低,一方面提高机体自噬可延缓细胞和组织衰老,另一方面自噬水平的过度激活可诱导细胞自噬性死亡、加速衰老。某些天然药物活性成分能调节自噬,并改善心血管系统衰老。它们可能是通过调节细胞自噬发挥对心血管系统衰老的保护作用。因此,文章就自噬在天然药物活性成分延缓心血管系统衰老中的作用及研究进展进行综述。 相似文献
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血管衰老是增龄相关性心血管疾病的主要危险因素,纤维化、钙化、慢性炎症、自噬水平下降、端粒缩短是血管衰老的重要诱因。转化生长因子β(TGF-β)是调节细胞生长和分化的重要细胞因子,其作为衰老相关分泌表型的成员在老龄机体内表达显著上调。在血管衰老进程中,TGF-β信号通路能够通过对血管纤维化、血管钙化、细胞自噬、炎症反应、端粒长度、端粒酶活性以及新型长寿靶点的调控影响血管衰老,从而在血管衰老相关疾病中发挥作用。 相似文献
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细胞自噬对衰老的调节 总被引:1,自引:0,他引:1
细胞内损伤物质的积累是所有衰老细胞的普遍特征,能导致生命有机体生存能力降低.细胞自噬能够降解受损蛋白质和衰老或损伤细胞器等细胞结构,是细胞内主要的异化途径,参与衰老以及与衰老相关的各种病理过程.近年来研究发现,衰老进程中,细胞自噬活动下调,而对各种长寿突变体的研究表明自噬活动是寿命延长所必需的,多种自噬相关基因或蛋白直接受长寿途径的调节[1~5],这些发现都支持细胞自噬是各种真核生物衰老非常重要的调节机制. 相似文献
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肾脏衰老是老年肾脏疾病的基础。机体内环境通过调控器官细胞凋亡、自噬、炎症以及再生修复进而影响器官的衰老。本文结合自身团队关于内环境影响肾脏衰老的研究工作,全面复习国内外相关文献,介绍内环境影响肾脏衰老的动物模型以及影响肾脏衰老和老年肾脏疾病的相关机制,并对内环境影响肾脏衰老的远期研究提出设想,旨在为相关基础研究和临床转化提供借鉴和参考。 相似文献
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范芸 《肾脏病与透析肾移植杂志》2012,21(3):268-273
自噬是由溶酶体介导的蛋白质和细胞器的降解过程,参与清除衰老的细胞器及破坏的蛋白质,维持细胞内环境稳定.自噬现象高度保守,几乎存在于所有物种,广泛作用于细胞生长、增生及肿瘤发生等过程.正常肾组织也存在基础自噬,近年有研究报道自噬异常可导致肾脏固有细胞损伤及多种肾脏疾病,人们已逐渐认识到自噬在肾脏疾病发生发展中的作用.本文就自噬及其在肾脏疾病中的相关研究加以综述,从而为相关疾病的机制研究及治疗提供新思路. 相似文献
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Selman M Rojas M Mora AL Pardo A 《Seminars in respiratory and critical care medicine》2010,31(5):607-617
Aging is a natural process characterized by a progressive functional impairment and reduced capacity to respond adaptively to environmental stimuli. Aging is associated with increased susceptibility to a variety of chronic diseases, including type 2 diabetes mellitus, cancer, and neurological diseases. Lung pathologies are not the exception, and the prevalence of several interstitial lung diseases (ILDs), primarily idiopathic pulmonary fibrosis, has been found to increase considerably with age. Although our understanding of the biology of aging has advanced remarkably in the last 2 decades, the molecular mechanisms linking aging to ILD remain unclear. Immunosenescence, oxidative stress, abnormal shortening of telomeres, apoptosis, and epigenetic changes affecting gene expression have been proposed to contribute to the aging process, and aging-associated diseases. Here, we review the emerging concepts highlighting the putative aging-associated abnormalities involved in some human ILDs. 相似文献
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Horan MP Pichaud N Ballard JW 《The journals of gerontology. Series A, Biological sciences and medical sciences》2012,67(10):1022-1035
There is accumulating evidence that mitochondrial respiratory malfunction is associated with aging-associated complex diseases. However, progress in our understanding of these diseases has been hampered by the sensitivity and throughput of systems employed to quantify dysfunction and inherent limitations of the biological systems studied. In this review, we describe and contrast two methodologies that have been developed for measuring mitochondrial function to address the need for improved sensitivity and increased throughput. We then consider the utility of each methodology in studying three biological systems: isolated mitochondria, cultured cells, and cell fibers and tissues. Finally, we discuss the application of each methodology in the study of mitochondrial dysfunction in Alzheimer's disease, type 2 diabetes mellitus, and aging-associated autophagy impairment and mitochondrial malfunction. We conclude that the methodologies are complementary, and researchers may need to examine multiple biological systems to unravel complex diseases of aging. 相似文献
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Thrombotic cardiovascular diseases increase in incidence in the elderly, a tendency dependent on the age-related changes in vascular and hemostatic systems that include platelets, coagulation, and fibrinolytic factors as well as in the endothelium. The hypercoagulability of and advanced sclerotic changes in the vascular wall may contribute to the increased incidence of thrombosis in the elderly. One of the important key genes for aging-associated thrombosis is plasminogen activator inhibitor-1 (PAI-1), a principal inhibitor of fibrinolysis. The expression of PAI-1 is not only elevated in the elderly but also significantly induced in a variety of pathologies associated with the process of aging. These conditions include obesity, insulin resistance, emotional stress, immune responses, and vascular sclerosis/remodeling. Several cytokines and hormones, including tumor necrosis factor-alpha, transforming growth factor-beta, angiotensin II, and insulin, positively regulate the gene expression of PAI-1. The recent epidemic in obesity with aging in the industrialized society may heighten the risk for thrombotic cardiovascular disease because adipose tissue is a primary source of PAI-1 and cytokines. Emotional or psychosocial stress and inflammation also cause the elevated expression of PAI-1 in an age-specific pattern. Thus, PAI-1 could play a key role in the progression of cardiovascular aging by promoting thrombosis and vascular (athero)sclerosis. Further studies on the genetic mechanism of aging-associated PAI-1 induction will be necessary to define the basis for cardiovascular aging in relation to thrombosis. 相似文献
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One theory that attempts to explain how and why an organism ages is the developmental hypothesis of aging (DevAge), which
describes how developmental programming leads to aging in adults. Interestingly, the developmental origins of health and disease
hypothesis (DOHaD) asserts that some aging-associated diseases that occur in adults are closely related to development and
to conditions in the intrauterine environment. Thus, both aging and aging-associated diseases can be viewed, at least in part,
as the result of a developmental program that is activated early in embryogenesis and persists throughout the lifespan of
the organism. We would expect this developmental program to be regulated by a set of interacting protein networks that connect
environmental and molecular signals. However, the connection between aging and development is not clear. Thus, a systems biology
approach that incorporates different “omic” databases for two mammalian models, Homo sapiens and Mus musculus, was used to evaluate how development and aging are interconnected. Interestingly, three major, evolutionarily conserved
processes, namely the immune system, epigenetics, and aerobic metabolism, appear to regulate aging and development in both
H. sapiens and M. musculus. Considering that these three processes are essential to embryogenesis, the protein networks within these processes are subjected
to strong selective pressure to eliminate gross developmental abnormalities in early embryogenesis. This selective pressure
becomes more relaxed in the adult organism, permitting the onset of aging-associated diseases and inflammation-related aging;
this concept echoes the antagonistic pleiotropy hypothesis of aging. 相似文献
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Cells respond to changes in their environment and in their intracellular milieu by altering specific pathways of protein synthesis and degradation. Autophagy is a highly conserved catabolic process involved in the degradation of long-lived proteins, damaged organelles, and subcellular structures. The process is orchestrated by the autophagy related protein (Atg) to form the double-membrane structure autophagosomes, which then fuse with lysosomes to generate autophagolysosomes where subcellular contents are degraded for a variety of cellular processes. Alterations in autophagy play an important role in diseases including cancer, neurodegenerative diseases, aging, metabolic diseases, inflammation and cardiovascular diseases. In the latter, dysregulated autophagy is speculated to contribute to the onset and development of atherosclerosis, ischemia/reperfusion injury, cardiomyopathy, diabetes mellitus, and hypertension. Autophagy may be both adaptive and beneficial for cell survival, or maladaptive and detrimental for the cell. Basal autophagy plays an essential role in the maintenance of cellular homeostasis whereas excessive autophagy may lead to autophagic cell death. The point and counterpoint discussion highlights adaptive vs. maladaptive autophagy. In this review, we discuss the molecular control of autophagy, focusing particularly on the regulation of physiologic vs. defective autophagy. 相似文献
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Alessandro Bitto Chad A. Lerner Timothy Nacarelli Elizabeth Crowe Claudio Torres Christian Sell 《Age (Dordrecht, Netherlands)》2014,36(3):1123-1137
Advanced age is characterized by increased incidence of many chronic, noninfectious diseases that impair the quality of living of the elderly and pose a major burden on the healthcare systems of developed countries. These diseases are characterized by impaired or altered function at the tissue and cellular level, which is a hallmark of the aging process. Age-related impairments are likely due to loss of homeostasis at the cellular level, which leads to the accumulation of dysfunctional organelles and damaged macromolecules, such as proteins, lipids, and nucleic acids. Intriguingly, aging and age-related diseases can be delayed by modulating nutrient signaling pathways converging on the target of rapamycin (TOR) kinase, either by genetic or dietary intervention. TOR signaling influences aging through several potential mechanisms, such as autophagy, a degradation pathway that clears the dysfunctional organelles and damaged macromolecules that accumulate with aging. Autophagy substrates are targeted for degradation by associating with p62/SQSTM1, a multidomain protein that interacts with the autophagy machinery. p62/SQSTM1 is involved in several cellular processes, and its loss has been linked to accelerated aging and to age-related pathologies. In this review, we describe p62/SQSTM1, its role in autophagy and in signaling pathways, and its emerging role in aging and age-associated pathologies. Finally, we propose p62/SQSTM1 as a novel target for aging studies and age-extending interventions. 相似文献
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Makrantonaki E Zouboulis CC;German National Genome Research Network 《Experimental gerontology》2007,42(9):879-886
As our society is growing older, the consequences of aging have begun to gain particular attention. Improvement of quality of life at old age and prevention of age-associated diseases have become the main focus of the aging research. The process of aging in humans is complex and underlies multiple influences, with the probable involvement of heritable and various environmental factors. In particular, hormones are decisively involved in the generation of aging. Over time, important circulating hormones decline due to a reduced secretion of the pituitary, the adrenal glands and the gonads or due to an intercurrent disease. Among them, serum levels of growth factors and sexual steroids show significant aging-associated changes. Within the scope of the Explorative Project 'Genetic aetiology of human longevity' supported by the German National Genome Research Network 2 (NGFN-2) an in vitro model of human hormonal aging has been developed. Human SZ95 sebocytes were maintained under a hormone-substituted environment consisting of growth factors and sexual steroids in concentrations corresponding to those circulating in 20- and in 60-year-old women. Eight hundred and ninety-nine genes showed a differential expression in SZ95 sebocytes maintained under the 20- and 60-year-old hormone mixture, respectively. Among them genes were regulated which are involved in biological processes which are all hallmarks of aging. The most significantly altered signaling pathway identified was that of the transforming growth factor-beta (TGF-beta). A disturbed function of this cascade has been associated with tumorigenesis, i.e. in pancreatic, prostate, intestine, breast, and uterine cancer. Interestingly, genes expressed in signaling pathways operative in age-associated diseases such as Huntington's disease (HD), dentatorubral-pallidoluysian atrophy (DRPLA), and amyotrophic lateral sclerosis (ALS) were also identified. These data demonstrate that skin and its appendages may represent an adequate model for aging research. Hormones interact in a complex fashion, and aging may be partly attributed to the changes in their circulating blood levels. Furthermore, a disturbed hormone status may partially act towards the manifestation of neurodegenerative diseases. Thus, these results could be a basis for an integrated and interdisciplinary approach to the analysis of the aging process. 相似文献
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Aging is associated with various heart diseases, and this may be attributable, in part, to the prolonged exposure of the heart to cardiovascular risk factors. However, aging is also associated with heart disorders such as diastolic dysfunction that are not necessarily linked to the risk factors for cardiovascular diseases. Recent studies have demonstrated a mechanistic link between Wnt signaling and premature aging or aging-related phenotypes. As a part of the review series on Wnt signaling and the cardiovascular system, we discuss here the possible involvement of Wnt signaling in aging-associated heart diseases or heart disorders. 相似文献
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Jose A. Boga Beatriz Caballero Yaiza Potes Zulema Perez‐Martinez Russel J. Reiter Ignacio Vega‐Naredo Ana Coto‐Montes 《Journal of pineal research》2019,66(1)
There are several pathologies, syndromes, and physiological processes in which autophagy is involved. This process of self‐digestion that cells trigger as a survival mechanism is complex and tightly regulated, according to the homeostatic conditions of the organ. However, in all cases, its relationship with oxidative stress alterations is evident, following a pathway that suggests endoplasmic reticulum stress and/or mitochondrial changes. There is accumulating evidence of the beneficial role that melatonin has in the regulation and restoration of damaged autophagic processes. In this review, we focus on major physiological changes such as aging and essential pathologies including cancer, neurodegenerative diseases, viral infections and obesity, and document the essential role of melatonin in the regulation of autophagy in each of these different situations. 相似文献