血管衰老相关细胞模型的研究进展

近年来,人类寿命显著增加,人口老龄化现象越来越严重,以糖尿病、心血管疾病、痴呆和阿尔茨海默病为代表的增龄性疾病的发病率和死亡率逐年上升,人口老龄化严重影响了人类的身体健康和生活质量.衰老是生物体的必然结局,深入研究衰老及衰老相关疾病发生发展的机制,延缓衰老、减少衰老相关疾病的发生对人类健康事业具有重要意义.血管衰老是机...     

运动对生殖系统衰老机制的影响

衰老是一个任何人都无法避免的过程,也是身体各部分器官系统的功能逐渐衰退的过程,生殖系统的衰老逐渐成为了一个不容忽视的问题。众所周知,适量的运动有助于延缓衰老,但是不同的运动量对于生殖系统的影响是不同的。有研究表明,过量的运动不仅不能延缓生殖系统的衰老,反而对于性激素的分泌起到不利的作用。已有一些研究表明合适的运动强度对于延缓生殖系统衰老、治疗不育等方面具有重要的意义。     

蛋氨酸限制提高内源性H2S活性延缓衰老的机制研究进展

蛋氨酸限制(Methionine restriction,MetR)作为饮食限制的方法之一,能够改善多种无脊椎动物、啮齿类动物及包括人类灵长类动物的衰老及其相关疾病。但MetR对衰老的具体调节作用机制尚未完全明确,目前除了与饮食限制的共有机制以外,越来越多的研究表明内源性硫化氢(Endogenous hydrogen sulfide,H2S)可能是其发挥效应的主要机制。硫化氢作为水溶性和脂溶性的小分子气体,在延缓衰老进程和改善衰老相关疾病中具有重要意义。本文阐述了MetR通过提高内源性H2S的活性延缓衰老的机制及相关研究。     

硫化氢对老年小鼠主动脉内皮衰老的影响北大核心CSCD

目的:探讨外源性硫化氢对老年小鼠主动脉内皮衰老的影响及可能机制。方法:8只3月龄雌性C57BL/6小鼠为对照组,16只22月龄雌性老年小鼠随机分为模型组和实验组,分别腹腔注射NaHS或生理盐水处理6周,检测相应指标,验证硫化氢对老年小鼠炎症、氧化应激及主动脉内皮衰老的作用。结果:与对照组相比,模型组小鼠体内细胞黏附分子-1(ICAM-1)和丙二醛(MDA)表达显著增加,超氧化物歧化酶1(SOD1)、内皮型一氧化氮合酶(eNOS)和一氧化氮(NO)表达明显减少,衰老相关标志物纤溶酶原激活物抑制剂-1(PAI-1)表达和衰老相关β-半乳糖苷酶(SA-β-Gal)染色比例明显升高。给予NaHS处理后,前述指标均得到一定程度逆转。结论:硫化氢可能通过抑制老年小鼠体内炎症反应和氧化应激改善主动脉内皮衰老。     

AMPK通过抑制NLRP3炎症小体参与延缓衰老过程

衰老是在细胞、组织和器官水平上发生的生理性内稳态的渐进性损害过程。就代谢角度而言,该过程主要表现为体成分、胰岛素抵抗、自噬功能障碍、线粒体和炎症反应的变化,其中涉及生长激素、胰岛素/胰岛素样生长因子1及各种能量感应系统如AMP活化蛋白激酶(AMP-activated protein kinase,AMPK).     

免疫衰老的研究进展

目前的研究认为,免疫衰老并非不可避免的逐进性退化过程,而是一个漫长的重塑结果.其中大部分免疫功能发生了退行性下降,但是少部分改变不显著,甚至略有加强.免疫衰老是一个与年龄相关的改变,累及非常复杂的机制,包括中枢免疫器官,外周免疫器官和细胞以及免疫分子的各个部分,从免疫细胞在中枢免疫器官的生成至造血干细胞到外周血淋巴细胞的转移、成熟以及增殖、分化、活化的各个阶段.免疫衰老引起的淋巴系统和细胞的功能紊乱,明显地影响了老年人的健康、疾病和死亡.对免疫衰老随龄性改变进行研究,旨在更好地预防老年随龄性疾病的发生发展,进而改善老年人群的生存质量和寿命.     

衰老的表观遗传学

衰老研究是生命科学和医学研究中最重要的领域之一,近年来衰老领域若干研究方面取得了令人鼓舞的进展,其中一个重要方面就是衰老的表观遗传学,本篇综述阐述了这一领域的最新进展,包括表观遗传在细胞和器官衰老中的角色,衰老的表观遗传失调节,几种与衰老相关分子的表观遗传学,如PASG、EZH2、PcG和端粒酶,另外还阐述了衰老过程中的印记异常,以及肾脏衰老的分子事件.     

多胺-eIF5A-羟腐胺赖氨酸化通路与衰老及相关疾病的研究进展

<正>随着全球人口逐渐老龄化，延缓衰老及防治其相关疾病成为迫切需要解决的社会问题。衰老是一种容易引发多种疾病的病理过程，衰老与这些疾病之间存在共同发生机制。因此，探索衰老及其相关疾病的发生机制和寻求高效的抗衰老药物已成为当前研究的热点。真核翻译起始因子5A(eukaryotic translation initiation factor 5A, eIF5A)是受羟腐胺赖氨酸化（hypusination）调节的一种翻译起始因子，多胺中的亚精胺（spermidine, SPD）是eIF5A发生羟腐胺赖氨酸化修饰的底物。     

衰老的分子机制

衰老是人类生命过程中的必然规律,但并不意味着人类在自身衰老方面无所作为,长期以来,人类都梦想着延缓衰老,延长寿命,近年来在细胞生物学和分子生物学迅速发展的推动下,衰老机理研究已取得重大进展,抗衰老研究已成为生命科学和医学领域的前沿课题,本文对近年来在衰老领域的最新进展作一综述。     

延缓衰老的“十要十不要”

心理衰老是自然规律,不可抗拒。但是,衰老的速度是可以通过自我调节和加强锻炼而延缓的。综合国内外资料,如能坚持以下十条办法,就可延缓心理衰老。     

Molecular inflammation: underpinnings of aging and age-related diseases

Recent scientific studies have advanced the notion of chronic inflammation as a major risk factor underlying aging and age-related diseases. In this review, low-grade, unresolved, molecular inflammation is described as an underlying mechanism of aging and age-related diseases, which may serve as a bridge between normal aging and age-related pathological processes. Accumulated data strongly suggest that continuous (chronic) upregulation of pro-inflammatory mediators (e.g., TNF-α, IL-1β, IL-6, COX-2, iNOS) are induced during the aging process due to an age-related redox imbalance that activates many pro-inflammatory signaling pathways, including the NF-κB signaling pathway. These pro-inflammatory molecular events are discussed in relation to their role as basic mechanisms underlying aging and age-related diseases. Further, the anti-inflammatory actions of aging-retarding caloric restriction and exercise are reviewed. Thus, the purpose of this review is to describe the molecular roles of age-related physiological functional declines and the accompanying chronic diseases associated with aging. This new view on the role of molecular inflammation as a mechanism of aging and age-related pathogenesis can provide insights into potential interventions that may affect the aging process and reduce age-related diseases, thereby promoting healthy longevity.     

Drivers of age-related inflammation and strategies for healthspan extension

Aging is the greatest risk factor for the development of chronic diseases such as arthritis, type 2 diabetes, cardiovascular disease, kidney disease, Alzheimer's disease, macular degeneration, frailty, and certain forms of cancers. It is widely regarded that chronic inflammation may be a common link in all these age-related diseases. This raises the question, can one alter the course of aging and potentially slow the development of all chronic diseases by manipulating the mechanisms that cause age-related inflammation? Emerging evidence suggests that pro-inflammatory cytokines interleukin-1 (IL-1) and IL-18 show an age-dependent regulation implicating inflammasome-mediated caspase-1 activation in the aging process. The Nod-like receptor (NLR) family of innate immune cell sensors, such as the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome controls the caspase-1 activation in myeloid-lineage cells in several organs during aging. The NLRP3 inflammasome is especially relevant to aging as it can get activated in response to structurally diverse damage-associated molecular patterns (DAMPs) such as extracellular ATP, excess glucose, ceramides, amyloids, urate, and cholesterol crystals, all of which increase with age. Interestingly, reduction in NLRP3-mediated inflammation prevents age-related insulin resistance, bone loss, cognitive decline, and frailty. NLRP3 is a major driver of age-related inflammation and therefore dietary or pharmacological approaches to lower aberrant inflammasome activation holds promise in reducing multiple chronic diseases of age and may enhance healthspan.     

Inflammation, the complement system and the diseases of aging

Inflammation is characteristic of neurodegenerative diseases of aging. Neuropathological evidence of activated microglia and activated astrocytes in lesioned areas, combined with epidemiological evidence of sparing of Alzheimer's disease (AD), Parkinson's disease (PD) and age-related macular degeneration (AMD) in long-term users of anti-inflammatory agents, indicates that inflammation is autodestructive of neurons. Locally produced autodestructive molecules include the membrane attack complex (MAC) of complement and oxygen-free radicals. Stimulation is provided by a variety of inflammatory cytokines. Agents which reduce the intensity of inflammation should have broad spectrum application in degenerative diseases of aging.     

血管老化在动脉粥样硬化中的研究进展

血管老化是血管的结构和功能随年龄增长呈现年龄依赖性的退行性改变,可导致心血管疾病的患病风险显著增加.动脉粥样硬化是多种心血管疾病的病理生理基础,血管老化在动脉粥样硬化的发生发展中发挥重要作用.有效评估血管老化对动脉粥样硬化性心血管疾病的临床诊疗意义重大.本文总结了血管老化的结构和功能性变化,阐述血管老化过程中血管细胞端...     

Role of indoleamine 2,3-dioxygenase 1 (IDO1) and kynurenine pathway in the regulation of the aging process

Indoleamine 2,3-dioxygenase 1 (IDO1) is activated in chronic inflammatory states, e.g., in the aging process and age-related diseases. IDO1 enzyme catabolizes L-tryptophan (L-Trp) into kynurenine (KYN) thus stimulating the KYN pathway. The depletion of L-Trp inhibits the proliferation of immune cells in inflamed tissues and it also reduces serotonin synthesis predisposing to psychiatric disorders. Interestingly, IDO1 protein contains two immunoreceptor tyrosine-based inhibitory motifs (ITIM) which trigger suppressive signaling through the binding of PI3K p110 and SHP-1 proteins. This immunosuppressive activity is not dependent on the catalytic activity of IDO1. KYN and its metabolite, kynurenic acid (KYNA), are potent activators of the aryl hydrocarbon receptor (AhR) which can enhance immunosuppression. IDO1-KYN-AhR signaling counteracts excessive pro-inflammatory responses in acute inflammation but in chronic inflammatory states it has many harmful effects. A chronic low-grade inflammation is associated with the aging process, a state called inflammaging. There is substantial evidence that the activation of the IDO1-KYN-AhR pathway robustly increases with the aging process. The activation of IDO1-KYN-AhR signaling does not only suppress the functions of effector immune cells, probably promoting immunosenescence, but it also impairs autophagy, induces cellular senescence, and remodels the extracellular matrix as well as enhancing the development of osteoporosis and vascular diseases. I will review the function of IDO1-KYN-AhR signaling and discuss its activation with aging as an enhancer of the aging process.     

A preliminary investigation of attachment style and inflammation in African-American young adults

ABSTRACT

Individuals’ social experiences are associated with their mental health, physical health, and even mortality. Over the last 30 years, researchers have examined the ways in which these social experiences might be associated with chronic inflammation – a component underlying many of the chronic diseases of aging. Little research, however, has examined the role of adults’ attachment style as a specific social component that might be associated with inflammation. In the present study, we utilized data from a sample of 59 African-American adults from the Maryland Adolescent Development in Context Study (MADICS) to examine the links between attachment avoidance and attachment anxiety and C-reactive protein (CRP) and interleukin (IL)-6. After controlling for demographic characteristics, body mass index, and depressive symptoms, attachment avoidance and anxiety were associated with IL-6 but not CRP. This study adds to the growing body of research identifying the wide range of social experiences associated with inflammation and further suggests that attachment relationship experiences may have implications for biological processes relevant to many chronic diseases of aging.     

Cerebrovascular expression of proteins related to inflammation,oxidative stress and neurotoxicity is altered with aging

Background  

Most neurodegenerative diseases are age-related disorders; however, how aging predisposes the brain to disease has not been adequately addressed. The objective of this study is to determine whether expression of proteins in the cerebromicrovasculature related to inflammation, oxidative stress and neurotoxicity is altered with aging.