Mitochondrial quality control: The role of mitophagy in aging

Autophagy is a catabolic process for eliminating macromolecules and damaged organelles by a highly regulated lysosomal pathway. Importantly, autophagy serves as an integral quality control mechanism by recycling cellular constituents for energy consumption and cellular rejuvenation under basal and stress conditions. Nevertheless, there is growing evidence that under certain conditions autophagy can switch from an adaptive survival mechanism to maladaptive process that promotes cell death. Furthermore, defects in autophagy have been linked to mitochondria injury and cell death associated with aging. In this review, we describe the role of autophagy as a physiological mechanism for maintaining homeostasis with its specific involvement in mitochondrial quality control and cardiac aging.     

Common paraoxonase gene variants, mortality risk and fatal cardiovascular events in elderly subjects

Recent studies indicate that the enzyme paraoxonase may be an important modulator of cardiovascular disease risk because of its ability to protect LDL from oxidation. We tested for association between two functional variants of the paraoxonase gene (Met-55/Leu and Gln-192/Arg) and both all-cause mortality and fatal cardiovascular disease. This was done within a population-based study among subjects aged 85 years and over in a cross-sectional and a prospective design. In the cross-sectional analysis, the distribution of both paraoxonase genotypes was found to be similar in the subset of 364 elderly subjects who were born in Leiden, The Netherlands, as compared with 250 young subjects whose families originated from the same geographical region. The polymorphisms were in strong linkage disequilibrium (P<0.00001) and the frequency of the haplotype carrying both risk alleles was not lower in the elderly than in the young (0.313 vs. 0.284). The complete cohort of 666 elderly subjects was followed over 10 years. The risk of all-cause and cardiovascular mortality was not increased in elderly subjects with the paraoxonase Leu/Leu (RR, 1.1 [95% CI, 0.9-1.5] and 1.3 [95% CI, 0.8-2.0], respectively) or the Arg/Arg genotype (RR, 0. 9 [95% CI, 0.7-1.2] and 0.7 [95% CI, 0.4-1.3], respectively). In a subset of patients with diabetes, the all-cause mortality risk was elevated in Arg/Arg carriers (RR, 2.1 [95% CI, 0.8-5.8]) but this did not reach statistical significance. Analysis of genotype combinations did not yield significant associations with mortality. The paraoxonase gene variants, previously associated with coronary artery disease, are thus not likely to have a major effect on the risk of fatal cardiovascular disease in the population at large. Adverse effects of the gene variants might be observed in subjects exposed to factors that enhance oxidative stress such as diabetes.     

老年人微量白蛋白尿与心血管事件相关性探讨

目的探讨老年人微量白蛋白尿（MAU）与心帆管疾病危险性的关系。方法53例老年患者,按其尿白蛋白排泄量分为两组：正常白蛋白尿（NAU）组21例（尿白蛋白〈30mg,L）、MAU组32例（尿白蛋白30-300mg/L）,分析比较两组心血管事件及危险因素。结果与NAU组相比,MAU组患者具有高血压,高体重指数（BMI）、高血糖（Bs）、高三酰甘油（TG）、高低密度脂蛋白（LDL-C）等心血管危险因素,且冠状动脉造影（CAG）多支血管及弥漫性病变多,血管狭窄程度重,左室射血分数低,心肌梗死和心力衰竭的发生率高。结论MAU不仅是老年人肾脏损伤的标志,也是心血管事件独立的预测因子和危险因素。     

419例老年男性肾小球功能的增龄变化

目的 观察男性老年人群肾小球滤过率的增龄变化.方法 选择1996年1月至2006年1月间,在我院干部门诊连续查体的老年男性患者419例为研究对象,查阅体检及病历资料,记录逐年体格检查、血生化及影像学检查结果,用Cockcroft-Gault(C-G)公式及简化MDRD公式计算肾小球滤过率(GFR,单位:ml·min-1·1.73 m-2)及GFR的年平均下降速度.结果 (1)根据C-G公式(GFR1)及简化MDRD(GFR2)公式计算,GFR年平均下降速度分别为0.66和-0.07;(2)根据1996年年龄将419例分为60～69岁、70～79岁和80～89岁组,3组年平均GFR1下降速度分别为0.48±1.04、0.69±0.98和0.96±0.64;GFR2分别为-0.26±1.33、-0.06±1.43和0.27±1.26;(3)多元逐步回归分析显示,尿蛋白、基线年龄、基线GFR1值、高尿酸血症、体质量、基线血肌酐及贫血等是影响GFR下降速度的危险因素(P＜0.05);(4)Pearson相关分析显示,C-G公式与年龄和体质量的相关系数分别为-0.653(P＜0.01)、0.630(P＜0.01),MDRD公式分别为-0.214(P＜0.01)与-0.035(P＞0.05).结论 老年男性随增龄GFR年平均下降速度为0.66,且有加速趋势.     

Prevention of cardiovascular events in elderly hypercholesterolemic patients

The management of hyperlipidemia in the elderly patient is a major problem, given the frequency of dyslipidemias and cardiovascular disorders in this age group. Therapy must take current uncertainties into account and, in the absence of therapeutic studies carried out in the elderly, is typically based upon a case-by-case approach. Raised cholesterol levels remain a significant risk factor for coronary heart disease (CHD) in the elderly. Although the relative risk of CHD tends to diminish with increasing age, this reduction is accompanied by an increase in absolute risk (ie, the number of events) as the frequency of the illness increases markedly with age. The results of major outcome studies with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), when analyzed according to patient age, indicate that the benefits of these agents are not merely confined to younger individuals. However, the elderly form a unique patient population—the proportion of women is greater and the profile of cardiovascular illnesses is characterized, among others, by a greater incidence of cerebrovascular accidents. Problems relating to poor tolerability and comorbidity (which may give rise to drug-drug interactions) also occur more frequently in this age group. Moreover, the potential widespread treatment of hyperlipidemia in the elderly has profound economic implications. Under these circumstances, the clinical practice recommendations depend upon a reasonable extrapolation of epidemiologic and therapeutic data obtained from middle-aged men. At present, treatment is therefore aimed at patients with the most severe forms of hyperlipidemia, generally in the secondary prevention setting, taking into account the patient’s life expectancy. The results of ongoing studies will determine the benefits of lipid-lowering therapy for primary prevention of CHD in the elderly.     

Idiopathic deep venous thrombosis and arterial endothelial dysfunction in the elderly

Arterial and venous thrombosis have always been regarded as different pathologies and epidemiological studies have examined the association between venous thrombosis and indicators of atherosclerosis and/or arterial thromboembolic events. We measured the flow-mediated dilation (FMD), a well-known marker of arterial endothelial dysfunction, in young–middle-aged and old-aged patients with and without unprovoked deep venous thrombosis (DVT). The aim of this study was to investigate whether DVT was a significant predictor for impaired FMD, considering all the patients and young–middle-aged (age < 65 years) and old-aged (age ≥ 65 years) patients separately. FMD was measured in the brachial artery on a population of 120 subjects with the same atherosclerosis risk factors, 68 male and 52 female, 70 young–middle-aged subjects (mean age ± SD 49.5 ± 10.5 years) and 50 old-aged subjects (76.2 ± 7.7 years). Patients with DVT showed a significant decrease of FMD compared to patients without DVT (6.8 ± 5.5% vs. 10.9 ± 3.5%, p < 0.001). Moreover, old-aged patients showed a significant decrease of FMD compared to the young–middle-aged subjects (7.4 ± 4.1% vs. 9.8 ± 5.3%, p = 0.005). In the whole study population, DVT was strongly associated with FMD (risk factors adjusted β = −4.14, p < 0.001). A significant interaction between age and the presence of DVT on predicting FMD was found (p = 0.003) suggesting a differential behavior of DVT as predictor of FMD. In young–middle-aged group, multivariate model confirmed that DVT was the most significant predictor of continuous FMD (β = −6.06, p < 0.001). On the contrary, DVT was no more a predictor of FMD in the old age group (β = −0.73, p=0.556). Furthermore, old-aged patients without DVT showed a statistically significant decrease of FMD compared to the young–middle-aged subjects without DVT (8.2±2.1% vs. 12.6±2.7%, p<0.001) and old-aged patients with DVT showed a not statistically significant decrease of the FMD compared to the young–middle-aged patients with DVT (6.7±5.3% vs. 6.8±5.7%, p = 0.932). In conclusion, young–middle-aged patients with spontaneous DVT show an impaired FMD, whereas this impairment in old-aged subjects is evident independently from the presence or absence of DVT. Aging per se may be associated with physiologic abnormalities in the systemic arteries and with endothelial dysfunction.     

Oxidative stress induces gastric submucosal arteriolar dysfunction in the elderly

AIM:To evaluate human gastric submucosal vascular dysfunction and its mechanism during the aging process.METHODS:Twenty male patients undergoing subtotal gastrectomy were enrolled in this study.Young and elderly patient groups aged 25-40 years and 60-85 years,respectively,were included.Inclusion criteria were:no clinical evidence of cardiovascular,renal or diabetic diseases.Conventional clinical examinations were carried out.After surgery,gastric submucosal arteries were immediately dissected free of fat and connective tissue.Vascular responses to acetylcholine(ACh)and sodium nitroprusside(SNP)were measured by isolated vascular perfusion.Morphological changes in the gastric mucosal vessels were observed by hematoxylin and eosin(HE)staining and Verhoeff van Gieson(EVG)staining.The expression of xanthine oxidase(XO)and manganese-superoxide dismutase(Mn-SOD)was assessed by Western blotting analysis.The malondialdehyde(MDA)and hydrogen peroxide(H2O2)content and the activities of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)were determined according to commercial kits.RESULTS:The overall structure of vessel walls was shown by HE and EVG staining,respectively.Disruption of the internal elastic lamina or neointimal layers was not observed in vessels from young or elderly patients;however,cell layer number in the vessel wall increased significantly in the elderly group.Compared with submucosal arteries in young patients,the amount of vascular collagen fibers,lumen diameter and media cross-sectional area were significantly increased in elderly patients.Ach-and SNP-induced vasodilatation in elderly arterioles was significantly decreased compared with that of gastric submucosal arterioles from young patients.Compared with the young group,the expression of XO and the contents of MDA and H2O2in gastric submucosal arterioles were increased in the elderly group.In addition,the expression of Mn-SOD and the activities of SOD and GSH-Px in the elderly group decreased significantly compared with those in the young gr     

Arginine impairs endothelial and executive function in older subjects with cardiovascular risk

Neurovascular coupling, the relationship between cerebral blood flow and neuronal activity, is attenuated in patients with impaired executive function. We tested the hypothesis that peripheral vascular function may associate with executive function in older subjects with cardiovascular risk factors and that treatment with the antioxidant L-arginine would improve both vascular and executive function. Nineteen subjects with type 2 diabetes mellitus and/or controlled hypertension were enrolled. Subjects were treated with L-arginine or placebo for 4 days in a randomized, double-blinded, cross-over study. Brachial artery vascular function, peripheral artery tonometry, and Trail Making Test Part B testing were performed on day 1 and day 4 during each condition. L-arginine significantly reduced the digital reactive hyperemia index, and the comparison of changes against placebo was significant (P = .01). With executive function testing, we observed a significant interaction between treatment and order. Restricting the analysis to the first treatment period, subjects treated with placebo decreased their Trail Making Test Part B times by 57.3 ± 52.5 seconds from day 1 to day 4 (P = .01) while those treated with arginine had no significant change (6.4 ± 18.4 seconds worse, P = .37). In addition, L-arginine was associated with increased mean arterial pressure from 88 ± 9 mm Hg to 92 ± 11 mm Hg, which trended toward significance. L-arginine treatment worsened digital microvascular and executive function in older subjects with cardiovascular risk factors. These data further support a link between vascular and executive function.     

Endothelial function and cardiovascular events in chronic kidney disease

Background

As patients with chronic kidney disease (CKD) are at high risk of developing coronary artery disease (CAD), it is important to stratify their cardiovascular risk. We investigated whether peripheral endothelial dysfunction is associated with the presence of CAD in patients with CKD and is a predictor of cardiovascular events.

Methods

We enrolled 383 CKD patients with at least one coronary risk factor. Peripheral endothelial function was assessed by reactive hyperemia peripheral arterial tonometry index (RHI). The presence of CAD was determined by coronary angiography. Cardiovascular events were assessed during follow-up.

Results

Ln-RHI was significantly lower in risk factor-matched CKD patients (n = 323) than risk factor-matched non-CKD patients (n = 323) (0.527 ± 0.192 vs. 0.580 ± 0.218, p = 0.001). In CKD patients (n = 383), Ln-RHI was significantly lower in CAD (0.499 ± 0.183, n = 262) than non-CAD (0.582 ± 0.206, n = 121) (p < 0.001) patients. Multivariate logistic regression analysis identified Ln-RHI as an independent factor associated with the presence of CAD (p = 0.001). During a mean follow-up period of 30 months, 90 cardiovascular events were recorded in CKD patients. Multivariate Cox hazard analysis identified low-Ln-RHI as an independent predictor of cardiovascular events (hazard ratio = 2.70, 95% confidence interval = 1.62–4.51, p < 0.001). The predictive value of combined Ln-RHI and Framingham risk score (FRS) was evaluated by net reclassification index (NRI) and C-statistics, which showed significant improvement (NRI = 22%, p < 0.001) (C-statistics: FRS = 0.49, FRS + Ln-RHI = 0.62, p = 0.005).

Conclusions

Endothelial function was significantly impaired in CKD patients and correlated with the presence of CAD. Severe endothelial dysfunction was an independent and incremental predictor of cardiovascular events in CKD.     

Predictors for development of multiple organ dysfunction syndrome in elderly patients with acute myocardial infarction

Multiple organ dysfunction syndrome (MODS) is one of the leading causes of death in ICU patients.However,there have been few studies on the role of MODS as a cause of death in patients with acute myocardial infarction (AMI),particularly in those at advanced age.Our study aimed to investigate the incidence and to identify the predicting factors of MODS in elderly patients with AMI.Methods We identified consecutive patients with AMI who were discharged from the Chinese PLA General Hospital between January 1993 to June 2006.Medical records of 800 consecutive patients aged 60 years or over were analyzed retrospectively.Multivariate logistic regression was used to determine factors predicting in-hospital development of MODS.Results Twenty-seven (3.4%) patients developed MODS within 30 days after AMI.Compared with patients without MODS,patients with MODS had higher in-hospital mortality rates (55.6% vs 11.6%,P＜0.001 ) and more frequent complications of cardiogenic shock (25.9% vs 6.2%,P＜0.001),heart failure (HF) (59.3% vs 18.2%,P＜0.001 ),cardiac arrhythmia (44.4% vs 26.4%,P＜0.05) and pneumonia (55.6% vs 16.3%,P＜0.001).Multivariate logistic regression analysis showed the major predictors for the occurrence of MODS secondary to AMI were advanced age (≥ 75 years,odds ratio 2.64,95% confidence interval [CI] 1.13 to 6.61),heart rate/＞ 100 bpm on admission (odds ratio 1.74,[CI] 1.14 to 2.64),in-hospital complication of HF (odds ratio 3.03,[CI] 1.26 to 7.26) and pneumonia (odds ratio 2.82,[CI] 1.18 to 6.77).Conclusions MODS is not the uncommon complication in elderly patients with AMI and is associated with poor prognosis.Advanced age,heart failure and pneumonia are predictors of the development of MODS in patients with AMI.(J Geriatr Cardiol 2008;5:199-202)     

增龄对大鼠阴茎勃起功能的影响

目的　探讨增龄在勃起功能障碍 ( ED)中的作用。方法　应用注射阿朴吗啡和电刺激海绵体神经的方法 ,观察低月龄大鼠与老龄大鼠阴茎勃起情况 ,采用免疫组化方法检测大鼠阴茎组织一氧化氮合酶 ( NOS)的染色情况。结果　注射阿朴吗啡后 ,老龄大鼠阴茎勃起次数要少于低月龄大鼠 ( P<0 .0 5) ;电刺激海绵体神经后 ,老龄组大鼠阴茎海绵体内压增幅与低月龄大鼠相近 ( P>0 .0 5) ,但勃起潜伏期延长 ( P<0 .0 5) ;组织化学染色显示低月龄大鼠阴茎组织 NOS的染色明显强于老龄大鼠。结论　增龄对大鼠阴茎勃起功能有一定的影响 ,主要表现在中枢调节及 NOS水平下降两方面     

Effect of a physical training program using the Pilates method on flexibility in elderly subjects

The adaptations of the human body resulting from the aging process especially loss of flexibility can increase the risk of falls and the risk of developing other health conditions. Exercise training, in particular the Pilates exercise method, has become an important form of physical activity that minimizes the deleterious effects of aging on flexibility. Few studies have evaluated the effect of this training method on body flexibility among elderly. We aimed to evaluate the effects of physical training using the Pilates method on body flexibility of elderly individuals. Eighteen elderly women and two elderly men (aged 70 ± 4 years) followed a 10-week Pilates training program. Individuals were recruited from the local community via open invitations. At study entry, none of them had limited mobility (walking requiring the use of walkers or canes). Furthermore, those with neurologic, muscular, or psychiatric disorders as well as those using an assistive device for ambulation were excluded secondary to limited participation. Flexibility assessment tests (flexion, extension, right and left tilt, and right and left rotation of the cervical and thoracolumbar spine; flexion, extension, abduction, and lateral and medial right and left rotation of the glenohumeral joint; flexion, extension, abduction, adduction, and lateral and medial rotation of the right and left hip; and flexion of the right and left knee) were performed by a blinded evaluator using a flexometer before and after the training period. All assessments were carried out at the same time of day. There was an observed increase in flexion (22.86 %; p < 0.001), extension (10.49 %; p < 0.036), and rotation to the left side (20.45 %; p < 0.019) of the cervical spine; flexion (16.45 %; p < 0.001), extension (23.74 %; p = 0.006), lateral bending right (39.52 %; p < 0.001) and left (38.02 %; p < 0.001), and right rotation (24.85 %; p < 0.001) and left (24.24 %; p < 0.001) of the thoracolumbar spine; flexion (right—8.80 %, p = 0.034; left—7.03 %, p = 0.050), abduction (right—20.69 %, p < 0.001; left—16.26 %, p = 0.005), and external rotation (right—116.07 % and left—143 %; p < 0.001 for both directions) of the glenohumeral joint; flexion (right—15.83 %, p = 0.050; left—9.55 %, p = 0.047) of the hips; and bending (right—14.20 %, p = 0.006; left—15.20 %, p = 0.017) the knees. The joint with the greatest magnitude of improvement was the thoracolumbar spine. Thus, this type of training may minimize the deleterious effects of aging and may improve the functionality of elderly individuals, which would reduce the likelihood of accidents (especially falls).     

老年呼吸机相关性肺炎患者发生心血管事件的影响因素

目的 分析老年呼吸机相关性肺炎(VAP)患者发生心血管事件(CVE)相关因素.方法 回顾性调查2017年1月至2020年9月于贵州医科大学第三附属医院发生的297例VAP患者临床资料,根据是否发生CVE分为CVE组与非CVE组,并对可能影响发生CVE的相关因素进行分析.采用SPSS 25.0软件进行数据分析.根据数据类...