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共17条结果
  • 1.

    【2hr】Age-related changes in motor unit firing pattern of vastus lateralis muscle during low-moderate contraction

    包量

    机译 低中度收缩期间股外侧肌运动单位放电模式的年龄相关变化
    摘要：Age-related changes in motor unit activation properties remain unclear for locomotor muscles such as quadriceps muscles, although these muscles are preferentially atrophied with aging and play important roles in daily living movements. The present study investigated and compared detailed motor unit firing characteristics for the vastus lateralis muscle during isometric contraction at low to moderate force levels in the elderly and young. Fourteen healthy elderly men and 15 healthy young men performed isometric ramp-up contraction to 70 % of the maximal voluntary contractions (MVC) during knee extension. Multichannel surface electromyograms were recorded from the vastus lateralis muscle using a two-dimensional grid of 64 electrodes and decomposed with the convolution kernel compensation technique to extract individual motor units. Motor unit firing rates in the young were significantly higher (~+29.7 %) than in the elderly (p < 0.05). There were significant differences in firing rates among motor units with different recruitment thresholds at each force level in the young (p < 0.05) but not in the elderly (p > 0.05). Firing rates at 60 % of the MVC force level for the motor units recruited at <20 % of MVC were significantly correlated with MVC force in the elderly (r = 0.885, p < 0.0001) but not in the young (r = 0.127, p > 0.05). These results suggest that the motor unit firing rate in the vastus lateralis muscle is affected by aging and muscle strength in the elderly and/or age-related strength loss is related to motor unit firing/recruitment properties.
  • 2.

    【2hr】Bisulfite oligonucleotide-capture sequencing for targeted base- and strand-specific absolute 5-methylcytosine quantitation

    包量

    机译 亚硫酸氢盐寡核苷酸捕获测序，用于靶向碱基和链特异性绝对5-甲基胞嘧啶定量
    摘要：Epigenetic regulation through DNA methylation (5mC) plays an important role in development, aging, and a variety of diseases. Genome-wide studies of base- and strand-specific 5mC are limited by the extensive sequencing required. Targeting bisulfite sequencing to specific genomic regions through sequence capture with complimentary oligonucleotide probes retains the advantages of bisulfite sequencing while focusing sequencing reads on regions of interest, enables analysis of more samples by decreasing the amount of sequence required per sample, and provides base- and strand-specific absolute quantitation of CG and non-CG methylation levels. As an example, an oligonucleotide capture set to interrogate 5mC levels in all rat RefSeq gene promoter regions (18,814) and CG islands, shores, and shelves (18,411) was generated. Validation using whole-genome methylation standards and biological samples demonstrates enrichment of the targeted regions and accurate base-specific quantitation of CG and non-CG methylation for both forward and reverse genomic strands. A total of 170 Mb of the rat genome is covered including 6.6 million CGs and over 67 million non-CG sites, while reducing the amount of sequencing required by ~85 % as compared to existing whole-genome sequencing methods. This oligonucleotide capture targeting approach and quantitative validation workflow can also be applied to any genome of interest.Electronic supplementary materialThe online version of this article (doi:10.1007/s11357-016-9914-1) contains supplementary material, which is available to authorized users.
  • 3.

    【2hr】Higher levels of phosphorylated Y1472 on GluN2B subunits in the frontal cortex of aged mice are associated with good spatial reference memory, but not cognitive flexibility

    包量

    机译 老年小鼠额叶皮质GluN2B亚基上较高水平的磷酸化Y1472与良好的空间参考记忆有关，但与认知灵活性无关
    摘要：The N-methyl-d-aspartate receptor (NMDAr) is particularly vulnerable to aging. The GluN2B subunit of the NMDAr, compared to other NMDAr subunits, suffers the greatest losses of expression in the aging brain, especially in the frontal cortex. While expression levels of GluN2B mRNA and protein in the aged brain are well documented, there has been little investigation into age-related posttranslational modifications of the subunit. In this study, we explored some of the mechanisms that may promote differences in the NMDAr complex in the frontal cortex of aged animals. Two ages of mice, 3 and 24 months, were behaviorally tested in the Morris water maze. The frontal cortex and hippocampus from each mouse were subjected to differential centrifugation followed by solubilization in Triton X-100. Proteins from Triton-insoluble membranes, Triton-soluble membranes, and intracellular membranes/cytosol were examined by Western blot. Higher levels of GluN2B tyrosine 1472 phosphorylation in frontal cortex synaptic fractions of old mice were associated with better reference learning but poorer cognitive flexibility. Levels of GluN2B phosphotyrosine 1336 remained steady, but there were greater levels of the calpain-induced 115 kDa GluN2B cleavage product on extrasynaptic membranes in these old good learners. There was an age-related increase in calpain activity, but it was not associated with better learning. These data highlight a unique aging change for aged mice with good spatial learning that might be detrimental to cognitive flexibility. This study also suggests that higher levels of truncated GluN2B on extrasynaptic membranes are not deleterious to spatial memory in aged mice.
  • 4.

    【2hr】Relation between aerobic fitness and brain structures in amnestic mild cognitive impairment elderly

    包量

    机译 健忘性轻度认知障碍老年人有氧健身与脑结构的关系
    摘要：Mild cognitive impairment (aMCI) is a clinical condition, with high risk to develop Alzheimer’s disease. Physical exercise may have positive effect on cognition and brain structure in older adults. However, it is still under research whether these influences are true on aMCI subjects with low Ab_42 and high total tau in cerebrospinal fluid (CSF), which is considered a biomarker for AD. Therefore, we aimed to investigate a possible relation between aerobic fitness (AF) and gray matter (GM) volume and AF and white matter (WM) integrity in aMCI with a CSF biomarker. Twenty-two participants with aMCI acquired the images on a 3.0-T MRI. AF was assessed by a graded exercise test on a treadmill. Voxel-based morphometry and tract-based spatial statistic methods were used to analyze the GM volume and WM microstructural integrity, respectively. We correlated AF and GM volume and WM integrity in aMCI (p < 0.05, FWE corrected, cluster with at least five voxels). There was a positive relation between AF and GM volume mostly in frontal superior cortex. In WM integrity, AF was positively correlated with fractional anisotropy and negatively correlated with mean diffusivity and radial diffusivity, all in the same tracts that interconnect frontal, temporal, parietal, and occipital areas (longitudinal fasciculus, fronto-occipital fasciculus, and corpus callosum). These results suggest that aerobic fitness may have a positive influence on protection of brain even in aMCI CSF biomarker, a high-risk population to convert to AD.
  • 5.

    【2hr】Common SIRT1 variants modify the effect of abdominal adipose tissue on aging-related lung function decline

    包量

    机译 常见的SIRT1变异体可改变腹部脂肪组织对衰老相关的肺功能下降的影响
    摘要：Lung function is an independent predictor of mortality and serves as an aging marker in never smokers. The protein sirtuin-1 of gene SIRT1 has profound anti-inflammatory effects and regulates metabolic pathways. Its suggested longevity effects on lower organisms remain poorly studied in humans. In 1132 never smokers of the population-based SAPALDIA cohort, we investigated associations between single nucleotide polymorphisms (SNPs; rs730821, rs10997868, rs10823116) of SIRT1 and aging-related lung function decline over 11 years in terms of change in forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced expiratory flow between 25 and 75 % of FVC (FEF25–75) using multiple linear regression models. Interactions between the SIRT1 SNPs and adiposity parameters (body mass index (BMI), its change and weight gain) were tested by including multiplicative interaction terms into the models. SIRT1 polymorphisms exhibited no main effects, but modified the association between obesity measures and FEV1/FVC and FEF25–75 decline (p = 0.009–0.046). Per risk allele, FEV1/FVC decline was accelerated up to −0.5 % (95 % CI −1.0 to 0 %) and −0.7 % (−1.3 to −0.2 %) over interquartile range increases in BMI (2.4 kg/m2) or weight (6.5 kg), respectively. For FEF25–75 decline, corresponding estimates were −57 mL/s (−117 to 4 mL/s) and −76 mL/s (−1429 to −9 mL/s). Interactions were not present in participants with genetically lowered C-reactive protein concentrations. Genetic variation in SIRT1 might therefore affect lung function and human longevity by modifying subclinical inflammation arising from abdominal adipose tissue.Electronic supplementary materialThe online version of this article (doi:10.1007/s11357-016-9917-y) contains supplementary material, which is available to authorized users.
  • 6.

    【2hr】Ankle proprioceptive acuity is associated with objective as well as self-report measures of balance, mobility, and physical function

    包量

    机译 踝关节本体感受性敏锐度与客观以及自我报告的平衡，活动能力和身体机能相关
    摘要：Ankle proprioceptive information is integrated by the central nervous system to generate and modulate muscle contractions for maintaining standing balance. This study evaluated the association of ankle joint proprioception with objective and self-report measures of balance, mobility, and physical function across the adult life span. Seven hundred and ninety participants (age range 24–97 years, 362 women) who completed ankle proprioception assessment between 2010 and 2014 were included in the present study from the population-based cohort of the Baltimore Longitudinal Study of Aging (BLSA), USA. Outcome measures included ankle joint proprioception measured as threshold for perception of passive movement (TPPM); single leg stance time; perceived difficulty for standing balance; usual, fastest, and narrow-path gait speed; walking index; short physical performance battery score; and self-reported activity restriction due to fear of falling. Descriptive variables included age, sex, body mass index, education, strength, and cognition. Analyses of covariance (ANCOVA) in general linear model (GLM) or multinomial logistic regression analyses were performed, as appropriate, to test the hypothesis that balance, mobility, and physical function were significantly different according to TPPM quintiles even after adjusting for relevant covariates. Those with TPPM >2.2° consistently demonstrated poor balance, mobility, and physical function. However, with increase in challenge (single leg stance, fastest walking speed, and SPPB), TPPM >1.4° was associated with significantly worse performance. In conclusion, ankle proprioceptive acuity has an overall graded relationship with objective and self-report measures of balance, mobility, and physical function. However, the cutoff proprioceptive acuity associated with substantial decline or inability to perform could depend on the challenge induced.
  • 7.

    【2hr】Multidimensional model of apathy in older adults using partial least squares—path modeling

    包量

    机译 使用偏最小二乘法的老年人冷漠的多维模型-路径建模
    摘要：Apathy defined as a mental state characterized by a lack of goal-directed behavior is prevalent and associated with poor functioning in older adults. The main objective of this study was to identify factors contributing to the distinct dimensions of apathy (cognitive, emotional, and behavioral) in older adults without dementia. One hundred and fifty participants (mean age, 80.42) completed self-rated questionnaires assessing apathy, emotional distress, anticipatory pleasure, motivational systems, physical functioning, quality of life, and cognitive functioning. Data were analyzed using partial least squares variance-based structural equation modeling in order to examine factors contributing to the three different dimensions of apathy in our sample. Overall, the different facets of apathy were associated with cognitive functioning, anticipatory pleasure, sensitivity to reward, and physical functioning, but the contribution of these different factors to the three dimensions of apathy differed significantly. More specifically, the impact of anticipatory pleasure and physical functioning was stronger for the cognitive than for emotional apathy. Conversely, the impact of sensibility to reward, although small, was slightly stronger on emotional apathy. Regarding behavioral apathy, again we found similar latent variables except for the cognitive functioning whose impact was not statistically significant. Our results highlight the need to take into account various mechanisms involved in the different facets of apathy in older adults without dementia, including not only cognitive factors but also motivational variables and aspects related to physical disability. Clinical implications are discussed.Electronic supplementary materialThe online version of this article (doi:10.1007/s11357-016-9916-z) contains supplementary material, which is available to authorized users.
  • 8.

    【2hr】Increased levels of hyper-stable protein aggregates in plasma of older adults

    包量

    机译 老年人血浆中超稳定蛋白聚集体水平增加
    摘要：Proteins that misfold into hyper-stable/degradation-resistant species during aging may accumulate and disrupt protein homeostasis (i.e., proteostasis), thereby posing a survival risk to any organism. Using the method diagonal two-dimensional (D2D) SDS-PAGE, which separates hyper-stable SDS-resistant proteins at a proteomics level, we analyzed the plasma of healthy young (<30 years) and older (60–80 years) adults. We discovered the presence of soluble SDS-resistant protein aggregates in the plasma of older adults, but found significantly lower levels in the plasma of young adults. We identified the inflammation-related chaperone protein haptoglobin as the main component of the hyper-stable aggregates. This observation is consistent with the growing link between accumulations of protein aggregates and aging across many organisms. It is plausible higher amounts of SDS-resistant protein aggregates in the plasma of older adults may reflect a compromise in proteostasis that may potentially indicate cellular aging and/or disease risk. The results of this study have implications for further understanding the link between aging and the accumulation of protein aggregates, as well as potential for the development of aging-related biomarkers. More broadly, this novel application of D2D SDS-PAGE may be used to identify, quantify, and characterize the degradation-resistant protein aggregates in human plasma or any biological system.Electronic supplementary materialThe online version of this article (doi:10.1007/s11357-016-9919-9) contains supplementary material, which is available to authorized users.
  • 9.

    【2hr】Effects of age and sex on neuromuscular-mechanical determinants of muscle strength

    包量

    机译 年龄和性别对肌肉力量神经肌肉力学决定因素的影响
    摘要：The aim of this study was to concurrently assess the effect of age on neuromuscular and mechanical properties in 24 young (23.6 ± 3.7 years) and 20 older (66.5 ± 3.8 years) healthy males and females. Maximal strength of knee extensors (KE) and flexors (KF), contractile rate of torque development (RTD) and neural activation of agonist-antagonist muscles (surface EMG) were examined during maximal voluntary isometric contraction (MVIC). Tissue stiffness (i.e. musculo-articular stiffness (MAS) and muscle stiffness (MS)) was examined via the free-oscillation technique, whereas muscle architecture (MA) of the vastus lateralis and subcutaneous fat were measured by ultrasonography. Males exhibited a greater age-related decline for KE (47.4 %) and KF (53.1 %) MVIC, and RTD (60.4 %) when compared to females (32.9, 42.6 and 34.0 %, respectively). Neural activation of agonist muscles during KE MVIC falls markedly with ageing; however, no age and sex effects were observed in the antagonist co-activation. MAS and MS were lower in elderly compared with young participants and in females compared with males. Regarding MA, main effects for age (young 23.0 ± 3.3 vs older 19.5 ± 2.0 mm) and sex (males 22.4 ± 3.5 vs females 20.4 ± 2.7 mm) were detected in muscle thickness. For fascicle length, there was an effect of age (young 104.6 ± 8.8 vs older 89.8 ± 10.5 mm), while for pennation angle, there was an effect of sex (males 13.3 ± 2.4 vs females 11.5 ± 1.7°). These findings suggest that both neuromuscular and mechanical declines are important contributors to the age-related loss of muscle strength/function but with some peculiar sex-related differences.
  • 10.

    【2hr】Microbial translocation and skeletal muscle in young and old vervet monkeys

    包量

    机译 幼小和成年黑长尾猴中的微生物易位和骨骼肌
    摘要：Intestinal barrier dysfunction leads to microbial translocation (MT) and inflammation in vertebrate and invertebrate animal models. Age is recently recognized as a factor leading to MT, and in some human and animal model studies, MT was associated with physical function. We evaluated sarcopenia, inflammation, MT biomarkers, and muscle insulin sensitivity in healthy female vervet monkeys (6–27 years old). Monkeys were fed consistent diets and had large and varied environments to facilitate physical activity, and stable social conditions. Aging led to sarcopenia as indicated by reduced walking speeds and muscle mass, but general metabolic health was similar in older monkeys (n = 25) as compared to younger ones (n = 26). When older monkeys were physically active, their MT burden approximated that in young monkeys; however, when older monkeys were sedentary, MT burden was dramatically increased. MT levels were positively associated with inflammatory burden and negatively associated with skeletal muscle insulin sensitivity. Time spent being active was positively associated with insulin sensitivity as expected, but this relationship was specifically modified by the individual monkey’s MT, not inflammatory burden. Our data supports clinical observations that MT interacts with physical function as a factor in healthy aging.Electronic supplementary materialThe online version of this article (doi:10.1007/s11357-016-9924-z) contains supplementary material, which is available to authorized users.
  • 11.

    【2hr】Inflammatory insult during pregnancy accelerates age-related behavioral and neurobiochemical changes in CD-1 mice

    包量

    机译 怀孕期间的炎症性损伤可加速CD-1小鼠与年龄相关的行为和神经生化变化
    摘要：Data shows that inflammation during pregnancy significantly exerts a long-term influence on offspring, such as increasing the risk of adult cognition decline in animals. However, it is unclear whether gestational inflammation affects the neurobehavioral and neurobiochemical outcomes in the mother-self during aging. In this study, pregnant CD-1 mice intraperitoneally received lipopolysaccharide (LPS) in two doses (25 and 50 g/kg, respectively) or normal saline daily during gestational days 15–17. At the age of 15 months, a battery of behavioral tasks was employed to evaluate their species-typical behaviors, sensorimotor ability, anxiety levels, and spatial learning and memory abilities. An immunohistochemical method was utilized preliminarily to detect neurobiochemical indicators consisting of amyloid-β, phosphorylated tau, presynaptic proteins synaptotagmin-1 and syntaxin-1, glial fibrillary acidic protein (GFAP), and histone-4 acetylation on the K8 site (H4K8ac). The behavioral results showed that LPS exposure during pregnancy exacerbated a decline in 15-month-old CD-1 mice’s abilities to nest, their sensorimotor and spatial learning and memory capabilities, and increased their anxiety levels. The neurobiochemical results indicated that gestational LPS exposure also intensified age-related hippocampal changes, including increased amyloid-β42, phosphorylated tau, synaptotagmin-1 and GFAP, and decreased syntaxin-1 and H4K8ac. Our results suggested that the inflammatory insult during pregnancy could be an important risk factor for the development of Alzheimer’s disease, and the H4K8 acetylation might play an important role in the underlying mechanism. This study offers a perspective for improving strategies that support healthy development and successful aging.Electronic supplementary materialThe online version of this article (doi:10.1007/s11357-016-9920-3) contains supplementary material, which is available to authorized users.
  • 12.

    【2hr】Testosterone delays vascular smooth muscle cell senescence and inhibits collagen synthesis via the Gas6/Axl signaling pathway

    包量

    机译 睾丸激素通过Gas6 / Axl信号通路延迟血管平滑肌细胞衰老并抑制胶原蛋白合成
    摘要：Testosterone deficiency is associated with a higher incidence of cardiovascular diseases in men. However, its effect on cell senescence, which plays a causal role in vascular aging, remains unclear. Here, we tested the hypothesis that testosterone alleviated vascular smooth muscle cell (VSMC) senescence and collagen synthesis via growth arrest-specific protein 6 (Gas6)/Axl- and Akt/FoxO1a-dependent pathways. Testosterone significantly ameliorated angiotensin II-induced VSMC senescence and collagen overexpression. In addition, testosterone inhibited angiotensin II-induced matrix metalloproteinase-2 (MMP-2) activity, which played a pivotal role in facilitating age-related collagen deposition. Testosterone increased the expression of tissue inhibitor of metalloproteinase-2 but decreased the expression of MMP-2 and membrane type-1 metalloproteinase which contributed to increase MMP-2 activity. The effects on VSMCs senescence and collagen synthesis were mediated by restoration of angiotensin II-induced downregulation of Gas6 and Axl expression and a subsequent reduction of Akt and FoxO1a phosphorylation. The effects of testosterone were reversed by a Gas6 blocker, Axl-Fc, and a specific inhibitor of Axl, R428. Treatment of VSMCs with PI3K inhibitor abrogated the downregulating effect of testosterone on MMP-2 activity. Furthermore, when FoxO1a expression was silenced by using a specific siRNA, the inhibitory effect of testosterone on MMP-2 activity was revered as well, that indicated this process was Akt/FoxO1a dependence. Taken together, Gas6/Axl and Akt/FoxO1a were involved in protective effects of testosterone on VSMCs senescence and collagen synthesis. Our results provide a novel mechanism underlying the protective effect of testosterone on vascular aging and may serve as a theoretical basis for testosterone replacement therapy.Electronic supplementary materialThe online version of this article (doi:10.1007/s11357-016-9910-5) contains supplementary material, which is available to authorized users.
  • 13.

    【2hr】Telomere attrition in beta and alpha cells with age

    包量

    机译 β和α细胞的端粒磨损随年龄增长
    摘要：We have reported telomere attrition in β and α cells of the pancreas in elderly patients with type 2 diabetes, but it has not been explored how the telomere lengths of these islet cells change according to age in normal subjects. To examine the telomere lengths of β and α cells in individuals without diabetes across a wide range of ages, we conducted measurement of the telomere lengths of human pancreatic β and α cells obtained from 104 autopsied subjects without diabetes ranging in age from 0 to 100 years. As an index of telomere lengths, the normalized telomere-centromere ratio (NTCR) was determined for β (NTCRβ) and α (NTCRα) cells by quantitative fluorescence in situ hybridization (Q-FISH). We found NTCRβ and NTCRα showed almost the same levels and both decreased according to age (p < 0.001 for both). NTCRs decreased more rapidly with age and were more widely distributed (p = 0.036 for NTCRβ, p < 0.001 for NTCRα) in subjects under 18 years of age than in subjects over 18 years. There was a positive correlation between NTCRβ and NTCRα only among adult subjects (p < 0.001). In conclusion, the telomeres of β and α cells become shortened with normal aging process.Electronic supplementary materialThe online version of this article (doi:10.1007/s11357-016-9923-0) contains supplementary material, which is available to authorized users.
  • 14.

    【2hr】Cristacarpin promotes ER stress-mediated ROS generation leading to premature senescence by activation of p21waf-1

    包量

    机译 Cristacarpin通过激活p21waf-1促进内质网应激介导的ROS生成，导致早衰
    摘要：Stress-induced premature senescence (SIPS) is quite similar to replicative senescence that is committed by cells exposed to various stress conditions viz. ultraviolet radiation (DNA damage), hydrogen peroxide (oxidative stress), chemotherapeutic agents (cytotoxic threat), etc. Here, we report that cristacarpin, a natural product obtained from the stem bark of Erythrina suberosa, promotes endoplasmic reticulum (ER) stress, leading to sub-lethal reactive oxygen species (ROS) generation and which eventually terminates by triggering senescence in pancreatic and breast cancer cells through blocking the cell cycle in the G1 phase. The majority of cristacarpin-treated cells responded to conventional SA-β-gal stains; showed characteristic p21waf1 upregulation along with enlarged and flattened morphology; and increased volume, granularity, and formation of heterochromatin foci—all of these features are the hallmarks of senescence. Inhibition of ROS generation by N-acetyl-l-cysteine (NAC) significantly reduced the expression of p21waf1, confirming that the modulation in p21waf1 by anti-proliferative cristacarpin was ROS dependent. Further, the elevation in p21waf1 expression in PANC-1 and MCF-7 cells was consistent with the decrease in the expression of Cdk-2 and cyclinD1. Here, we provide evidence that cristacarpin promotes senescence in a p53-independent manner. Moreover, cristacarpin treatment induced p38MAPK, indicating the ROS-dependent activation of the MAP kinase pathway, and thus abrogates the tumor growth in mouse allograft tumor model.Electronic supplementary materialThe online version of this article (doi:10.1007/s11357-016-9922-1) contains supplementary material, which is available to authorized users.
  • 15.

    【2hr】Factors producing over-selectivity in older individuals

    包量

    机译 导致老年人选择性过度的因素
    摘要：Stimulus over-selectivity describes a phenomenon where only a subset of the relevant stimuli present in the environment, control an individual’s behavior. The current experiment explored the degree to which over-selectivity increases in old age. The level of over-selectivity in a visual discrimination task in 60 individuals aged 60–89 years was assessed, as well as the degree to which this reflected attentional control. In addition, the intellectual functioning and cognitive flexibility of the participants were assessed. Results showed that, as age increased, three effects were revealed: levels of stimulus over-selectivity increased, IQ scores decreased, and cognitive flexibility decreased. However, over-selectivity was not related to IQ or cognitive flexibility, and appeared related most to attentional impairments. Thus, ageing is related to significant declines in effective stimulus control. These effects can have a serious impact on the physical and psychological health of old adults, as well as their quality of life, and, therefore, this area of research warrants further exploration. The results are discussed in relation to the attention-deficit and comparator theory of over-selectivity.
  • 16.

    【2hr】Association between gait characteristics and endothelial oxidative stress and inflammation in patients with symptomatic peripheral artery disease

    包量

    机译 有症状外周动脉疾病患者步态特征与内皮氧化应激和炎症之间的关系
    摘要：The aim of the study was to determine whether gait characteristics were associated with endothelial cell inflammation, oxidative stress, and apoptosis and with circulating biomarkers of inflammation and antioxidant capacity in older patients with symptomatic peripheral artery disease (PAD). Gait measurements of 231 symptomatic men and women with PAD were assessed during a 4-m walk test. Patients were further characterized on endothelial effects of circulating factors present in the sera using a cell culture-based bioassay on primary human arterial endothelial cells and on circulating inflammatory and vascular biomarkers. In a multivariate regression model for gait speed, the significant independent variables were age (p < 0.001), intercellular cell adhesion molecule-1 (ICAM-1) (p < 0.001), diabetes (p = 0.003), sex (p = 0.003), and history of cerebrovascular accidents (p = 0.021). In multivariate analyses for gait cadence, the significant independent predictors included high-sensitivity C-reactive protein (HsCRP) (p < 0.001), diabetes (p = 0.001), and hypertension (p = 0.001). In a multivariate regression model for gait stride length, the significant independent variables were HsCRP (p < 0.001), age (p < 0.001), ICAM-1 (p < 0.001), hypertension (p = 0.002), cellular reactive oxygen species production (p = 0.007), and sex (p = 0.008). Higher levels of circulating biomarkers of inflammation and endothelial cell oxidative stress were associated with slower gait speed, slower cadence, and shorter stride length in older symptomatic patients with PAD. Additionally, this profile of impaired gait was more evident in older patients, in women, and in those with diabetes, hypertension, and history of cerebrovascular accidents.
  • 17.

    【2hr】The trajectory of the blood DNA methylome ageing rate is largely set before adulthood: evidence from two longitudinal studies

    包量

    机译 血液DNA甲基化组衰老率的轨迹在成年之前已基本确定：两项纵向研究的证据
    摘要：The epigenetic clock, defined as the DNA methylome age (DNAmAge), is a candidate biomarker of ageing. In this study, we aimed to characterize the behaviour of this marker during the human lifespan in more detail using two follow-up cohorts (the Young Finns study, calendar age i.e. cAge range at baseline 15–24 years, 25-year-follow-up, N = 183; The Vitality 90+ study, cAge range at baseline 19–90 years, 4-year-follow-up, N = 48). We also aimed to assess the relationship between DNAmAge estimate and the blood cell distributions, as both of these measures are known to change as a function of age. The subjects’ DNAmAges were determined using Horvath’s calculator of epigenetic cAge. The estimate of the DNA methylome age acceleration (Δ-cAge-DNAmAge) demonstrated remarkable stability in both cohorts: the individual rank orders of the DNAmAges remained largely unchanged during the follow-ups. The blood cell distributions also demonstrated significant intra-individual correlation between the baseline and follow-up time points. Interestingly, the immunosenescence-associated features (CD8+CD28− and CD4+CD28− cell proportions and the CD4/CD8 cell ratio) were tightly associated with the estimate of the DNA methylome age. In summary, our data demonstrate that the general level of Δ-cAge-DNAmAge is fixed before adulthood and appears to be quite stationary thereafter, even in the oldest-old ages. Moreover, the blood DNAmAge estimate seems to be tightly associated with ageing-associated shifts in blood cell composition, especially with those that are the hallmarks of immunosenescence. Overall, these observations contribute to the understanding of the longitudinal aspects of the DNAmAge estimate.Electronic supplementary materialThe online version of this article (doi:10.1007/s11357-016-9927-9) contains supplementary material, which is available to authorized users.
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