老年人心力衰竭

老年人心力衰竭十分常见。高血压、冠心病及增龄引起的心肌退行性变是老年人心衰的主要病因。左心室肥厚、心肌纤维化、冠脉病变引起的心肌缺血导致心室收缩及功能障碍是心衰的重要病理生理学基础。血管紧张素转换酶抑制剂，β受体阻滞剂能降低心衰患者的死亡率。钙敏化剂及Ｎａ＾＋／Ｈ＾＋交换器１型抑制剂有希望成为治疗心衰的有效药物。     

增龄对小鼠心肌氧自由基浓度,超氧化物歧化酶活性及丙二醛…

以心肌氧自由基浓度，超氧化物歧化酶活性、丙二醛含量为指标，观察了增龄对心肌自由基反应的影响，结果表明：（１）心肌ＯＦＲ浓度随增龄上升，至１３、１７月龄时达到显著水平（Ｐ＜０．０５）；（２）心肌ＳＯＤ活性随增龄下降，至１３、１７月龄时达到显著水平（Ｐ＜０．０５）；（３）心肌ＭＤＡ含量随增龄而增加，至１３、１７月龄时增加显著（Ｐ＜０．０５，Ｏ＜０．０１）；（４）老年小鼠（１７月龄）心肌ＳＯＤ活性与ＯＦ     

大枣对D-半乳糖致衰老小鼠钙稳态影响的实验研究

目的　探讨大枣对维持细胞内钙稳态的作用及机制。方法　本实验以D 半乳糖致衰老小鼠为研究对象 ,分别以大、中、小剂量的大枣水煎剂灌胃 45d,测定了青年、老年小鼠红细胞超氧化物歧化酶 (SOD)活性 ,心肌线粒体内丙二醛 (MDA)含量 ,心肌细胞膜Na K ATPase、Ca2 ATPase活性 ,心肌组织及线粒体Ca2 含量变化 ,同时 ,观察不同剂量大枣对老年小鼠上述指标的影响。结果　红细胞SOD活性、心肌细胞膜Na K ATPase、Ca2 ATPase活性、心肌线粒体Ca2 含量变化随增龄而下降 ;心肌线粒体内MDA含量、心肌组织Ca2 含量随增龄而上升。大枣可提高小鼠红细胞SOD活性 ,心肌细胞膜Na K ATPase、Ca2 ATPase活性、心肌线粒体Ca2 含量 ,并能降低心肌线粒体内MDA含量、心肌组织Ca2 含量。在各给药组中以大枣大剂量组的作用最强。结论　 (1 )大枣能增强机体抗氧化能力 ,减少自由基对生物膜的损伤 ,维持细胞内钙稳态 ,具有一定的抗衰老作用 ;(2 )自由基与钙超载协同作用可能是导致衰老的重要原因。     

洛沙坦对心脏和动脉衰老保护作用的实验研究

目的观察老龄大鼠心肌纤维化程度、血管内皮依赖性舒张功能不全的变化及洛沙坦的干预作用,探讨血管紧张素II受体I(AT1R)拮抗剂(ARB)对心脏和动脉衰老的保护作用。方法Wistar大鼠30只,分为成年组、老龄组、洛沙坦组,生化法测心肌纤维化指标,免疫组化法测转化生长因子β1(TGFβ1)的表达。硝酸还原酶法测主动脉NO生成量,比色法测主动脉NOS活力。结果与成年组比较,老龄组心肌纤维化程度明显升高,TGFβ1表达上调,乙酰胆碱介导的内皮依赖性舒张反应受损(P<005),NO量及总NOS活力均显著降低(P<001)。与老龄组比较,洛沙坦组心肌纤维化程度明显降低(P<005),心肌TGFβ1表达减少,内皮依赖性舒张反应明显提高(P<001),NO量及总NOS活力均显著升高(P<005)。结论随着增龄,心肌纤维化程度增高,TGFβ1表达逐渐增加,血管内皮依赖性舒张功能减退。洛沙坦可抑制老龄大鼠心肌纤维化的形成,对增龄引起的血管内皮功能不良有改善作用。     

大鼠心肌组织中原癌基因（c—myc,Ha—ras,c—fos）表达的随龄性改变

目的　通过研究原癌基因(c-myc，Ha-ras，c-fos)在衰老心肌中的表达，探讨增龄对心肌生长相关的原癌基因的影响。方法　20月龄及6月龄健康雄性SD大鼠，以Northern杂交分析c-myc，Ha-ras，c-fos基因表达。结果　Ha-ras和c-fos在6月龄、20月龄大鼠心室肌中均表达，老龄鼠c-fos的表达水平明显高于青龄鼠(0.523±0.07，0.185±0.05)(P＜0.05)；c-Ha-ras则无显著差异(0.65±0.07，0.63±0.06)(P＞0.05)；c-myc在6月龄和20月龄大鼠心室肌中均无表达。结论　原癌基因((c-myc，Ha-ras，c-fos等)随增龄在心肌组织中的表达各不相同，探讨老年期中各基因重新激活和高表达的意义，有可能为老年心脏病的发生和心肌老化的内在机制提供一个新的解释。     

衰老心肌自噬减退的新机制-转录因子EB的关键作用

目的 探讨转录因子EB（TFEB）在衰老心肌自噬减退中的作用。方法 采用老年（22月龄）雄性C57BL/6小鼠为实验对象,以成年（4月龄）雄性C57BL/6小鼠为对照,分析心肌自噬水平、心肌TFEB表达水平。结果 与成年心肌相比,衰老心肌自噬水平显著降低（P<0.05）。衰老心肌中自噬体标志物Atg5、LC3和Beclin-1,溶酶体标志物LAMP1在蛋白和mRNA水平上均出现降低。与成年心肌相比,衰老心肌TFEB蛋白水平显著降低（P<0.05）,衰老心肌细胞核内的TFEB水平下降更为显著（P<0.05）,提示衰老心肌TFEB转录能力减退。给予小剂量雷帕霉素处理,可提高衰老心肌细胞核内TFEB水平,并且改善LC3及LAMP1的mRNA和蛋白水平,提高衰老心肌自噬水平。结论 本研究发现衰老导致的心肌TFEB水平降低严重影响心肌自噬能力,提示TFEB是心肌自噬增龄性减退机制中的关键调节因子。     

牙齿衰老的组织学 研究进展

随增龄牙齿亦发生结构和功能的改变。本文对牙釉质、牙本质、牙髓、牙周韧带及牙龈的增龄变化作一综述。     

从免疫观点看衰老

随增龄免疫功能变化的特点是对外源性抗原免疫应答降低和对自身免疫应答增强。本文介绍随增龄免疫功能在机体、脏器、组织、细胞、分子及基因水平的变化。     

心力衰竭中能量代谢紊乱及治疗的进展

心力衰竭是大多数心血管疾病的终末阶段,发病率和死亡率较高,严重危害人类的健康。心衰的发病机制复杂,尽管不同原发病导致心衰的机制存在差异,但心肌代谢异常、能量利用障碍是共同作用途径。目前改善心衰患者异常的心肌能量代谢已成为治疗心衰的有效手段,受到临床医生广泛关注。因此,本文就心衰与心肌能量代谢之间的关系及心肌能量代谢药物的应用进行综述,增进医务工作者对心衰及其治疗的理解。     

正电子发射断层显像评价衰老心肌葡萄糖代谢的变化

目的用正电子发射断层显像(positron emission computed tomography,PET)评估增龄对心肌葡萄糖代谢的影响。方法入选40例健康者,按照年龄分为成年组(40～59岁)和老年组(60～79岁),每组20例。所有研究对象进行静息心肌单光子发射计算机断层摄影(SPECT)和静息心肌PET,测定2组SPECT的左心室17节段静息总评分和各节段评分,与SPECT相匹配的各节段心肌的最大标准化摄取值(SUV_(max))。结果老年组与成年组左心室心肌SPECT的平均静息总评分差异无统计学意义(P0.05)。老年组前间隔基底部、下间隔中份、尖前壁和尖下壁静息评分较成年组明显增高(P0.05);老年组左心室各节段心肌~(18)F-脱氧葡萄糖(~(18)F-FDG)的总SUV_(max)较成年组明显增高(P0.01);老年组左心室多个节段的SUV_(max)较成年组明显增高,差异有统计学意义(P0.05,P0.01)。结论衰老可导致心肌对缺血敏感性加重的趋势;增龄可使心肌对~(18)F-FDP摄取和利用增加,可能是对衰老所致心肌缺血的自然保护性机制。     

Heart failure in older adults

Typical aging leads to insidious changes in the heart and throughout the body that predispose to heart failure (HF). HF with left ventricular systolic dysfunction and HF with preserved ejection fraction increase as a result of common age-related physiologic changes. Moreover, aging is associated with high comorbidity and high likelihood of iatrogenic side effects from therapeutic interventions that add to the complexity of HF management and contribute to patterns of particularly high HF mortality and morbidity. This article reviews key age-related mechanisms of HF pathophysiology and associated management challenges.     

Mitochondrial-nuclear Cross-talk in the Aging and Failing Heart

Hypothesis Damage to heart mitochondrial structure and function occur with aging, and in heart failure (HF). However, the extent of mitochondrial dysfunction, the expression of mitochondrial and nuclear genes, and their cross-talk is not known. Observations Several observations have suggested that somatic mutations in mitochondrial DNA (mtDNA), induced by reactive oxygen species (ROS), appear to be the primary cause of energy decline, and that the generation of ROS is mainly the product of the mitochondrial respiratory chain. The free radical theory of aging, that could also be applied to HF, and in particular the targeting of mtDNA is supported by a plurality of observations from both animal and clinical studies showing decreased mitochondrial function, increased ROS levels and mtDNA mutations in the aging heart. Discussion Aging and HF with their increased ROS-induced defects in mtDNA, including base modifications and frequency of mtDNA deletions, might be expected to cause increased errors or mutations in mtDNA-encoded enzyme subunits, resulting in impaired oxidative phosphorylation and defective electron transport chain (ETC) activity which in turn creates more ROS. These events in both the aging and failing heart involve substantial nuclear–mitochondrial interaction, which is further illustrated in the progression of myocardial apoptosis. In this review the cross-talk between the nucleus and the mitochondrial organelle will be examined based on a number of animal and clinical studies, including our own.     

A proton magnetic resonance spectroscopy study of aging and transformed human fibroblasts

Proton magnetic resonance spectroscopy (¹H MRS) has been used to monitor changes occurring during aging and transformation in human lung fibroblasts. Aging was studied in MRC-5 cells from nonsenescent (early passage) to presenescent (late passage) and senescence. Nonsenescent cells infected with SV40 virus (pretransformed) were monitored through crisis and subsequent immortalization. Aging changes were observed with one- and two-dimensional MR spectra. Cholesterol and lipid resonances were significantly increased from nonsenescent cultures to senescence. These changes could be caused by chemical or structural changes in the plasma membrane or in intracellular lipid pools. In contrast, choline levels rose from nonsenescent to presenescent cells but at senescence dropped to that of nonsenescent cells. Increased choline levels are often associated with increased cellular proliferation. After SV40 infection of MRC-5 cells there was an increase of cholesterol and lipid levels that peaked at crisis. Newly immortalized cells exhibited a drop in cholesterol and lipid to nonsenescent cell levels, but these rose again in established immortalized cells. In contrast to presensescent cultures, the levels of choline gradually increased from pretransformed to crisis phase but still continued to rise after immortalization. Thus, ¹H MRS illustrates similarities in lipid behavior at senescence and crisis, whereas the choline levels are different.     

睾酮对心脏老化过程中心肌纤维化的干预研究

目的观察睾酮对心脏老化过程中心肌纤维化的干预效应。方法差速贴壁法培养雄性昆明白乳鼠心肌成纤维细胞,并分为4组:A组(培养液)、B组(60 μmol/L H_2O_2)、C组(30 nmol/L 睾酮+B组)、D组(氟他胺1μmol/L+C组)。用β半乳糖苷酶染色检测细胞的阳性率,MTT法检测细胞增殖能力,流式细胞仪分析细胞周期,二氯荧光黄荧光显色检测细胞内活性氧(ROs)。α平滑肌肌动蛋白(α-SMA)免疫化学染色反应细胞的表型转化,RT-PCR法检测转化生长因子β1(TGF-β1)mRNA、P16 mRNA和cyclin D1 mRNA的表达。结果与A组比较.B组β-半乳糖苷酶染色阳性细胞增加,ROS水平增加,P16 mRNA、cyclin D1 mRNA、TGF-β1 mRNA表达上调,细胞增殖能力明显下降,G_0/G_1期细胞比例增多,同时α-SMA免疫组织化学染色出现明显强阳性;与B组比较,C组上述各项指标下降;与C组比较,D组能部分阻断睾酮的各种保护作用。结论睾酮通过受体机制干预氧化应激诱导的心肌成纤维细胞的衰老,这可能是睾酮抗心脏老化过程中心肌纤维化的机制之一。     

Telomeres and telomerase: basic science implications for aging

Life expectancy in the United States and other developed nations has increased remarkably over the past century, and continues to increase. However, lifespan has remained relatively unchanged over this period. As life expectancy approaches maximum human lifespan, further increase in life expectancy would only be possible if lifespan could also be increased. Although little is known about the aging process, increasing lifespan and delaying aging are the research challenges of the new century, and have caused intense debate and research activities among biogerontologists. Many theories have been proposed to explain the aging process. However, damage to deoxyribonucleic acid (DNA) is the centerpiece of most of these. Recently telomere shortening has been described to be associated with DNA damage. Located at the ends of eukaryotic chromosomes and synthesized by telomerase, telomeres maintain the length of chromosomes. The loss of telomeres can lead to DNA damage. The association between cellular senescence and telomere shortening in vitro is well established. In the laboratory, telomerase-negative differentiated somatic cells maintain a youthful state, instead of aging, when transfected with vectors encoding telomerase. Many human cancer cells demonstrate high telomerase activity. Evidence is also accumulating that telomere shortening is associated with cellular senescence in vivo. What causes changes in expression of telomerase in different cell types and premature aging syndromes? Does the key to "youthfulness" lie in our ability to control the expression of telomerase? We have reviewed the contemporary literature to find answers to these questions and explore the association between aging, telomeres, and telomerase.     

Interventional therapies for heart failure in the elderly

The aging of a population replete with risk factors for heart failure(HF) (coronary heart disease, diabetes, and hypertension) coupled with a declining age-adjusted mortality rate for coronary artery and hypertensive heart diseases has created, and will continue to create, a literal explosion in the prevalence of HF in the United States. Despite advances in maximal medical therapy, however, most patients who have symptomatic HF can expect functional impairment, interludes of worsening symptomatology, and a shortened lifespan. This article updates the use of interventional therapies for the treatment of elderly patients who have HF caused by coronary artery disease, valvular heart disease, congenital heart disease, myocardial disease, and renal vascular disease.     

Interventional therapies for heart failure in the elderly

The aging of a population replete with risk factors for heart failure (HF) (coronary heart disease, diabetes, and hypertension) coupled with a declining age-adjusted mortality rate for coronary artery and hypertensive heart diseases has created, and will continue to create, a literal explosion in the prevalence of HF in the United States. Despite advances in maximal medical therapy, however, most patients who have symptomatic HF can expect functional impairment, interludes of worsening symptomatology, and a shortened lifespan. This article updates the use of interventional therapies for the treatment of elderly patients who have HF caused by coronary artery disease, valvular heart disease, congenital heart disease, myocardial disease, and renal vascular disease.     

细胞衰老与肾移植

细胞衰老是生物老化进程的重要组成部分。越来越多的研究表明,细胞衰老的两条主要信号通路(p53和p16途径)在肾移植后肾脏病变的发生、发展及预测移植器官预后等方面,起到重要作用。本文简单总结目前关于细胞衰老分子机制方面的研究观点,并就其在肾移植领域的相关研究做一简单综述。     

Impact of miRNAs on cardiovascular aging

Aging is a multidimensional process that leads to an increased risk of developing severe diseases, such as cancer and cardiovascular, neurodegenerative, and immunological diseases. Recently, small non-coding RNAs known as microRNAs (miRNAs) have been shown to regulate gene expression, which contributes to many physiological and pathophysiological processes in humans. Increasing evidence suggests that changes in miRNA expression profiles contribute to cellular senescence, aging and aging-related diseases. However, only a few miRNAs whose functions have been elucidated have been associated with aging and/or aging-related diseases. This article reviews the currently available findings regarding the roles of aging-related miRNAs, with a focus on cardiac and cardiovascular aging.