Maintaining adequate levels of physical activity is known to preserve health status and functional independence as individuals grow older. However, the relationship between determinants of physical activity (volume and intensity) and physiological factors underlying mobility (cardio-respiratory fitness, neuromuscular function and functional abilities) is still unclear. The aim of this study was to investigate the association between objectively quantified physical activity and a spectrum of physiological factors underlying mobility in young, middle-aged and older individuals living in a city district. Experiments were carried out on 24 young (28±2 years), 24 middle-aged (48±2 years) and 24 older (70±3 years) gender-matched volunteers. Physical activity was monitored by a wearable activity monitor to quantify volume and intensity of overall physical activity and selected habitual activities over 24 hours. Ventilatory threshold was assessed during an incremental cycling test. Torque, muscle fiber conduction velocity and agonist-antagonist coactivation were measured during maximal voluntary contraction of knee extensors and flexors. Ground reaction forces were measured during sit-to-stand and counter-movement jump. K-means cluster analysis was used to classify the participants’ physical activity levels based on parameters of volume and intensity. Two clusters of physical activity volume (i.e., high and low volume) and three clusters of physical activity intensity (i.e. high, medium and low intensity) were identified in all participants. Cardio-respiratory fitness was associated with volume of overall physical activity as well as lying, sitting, standing, walking and stair climbing. On the other hand, neuromuscular function and functional abilities showed a significant association with intensity of overall physical activity as well as postural transition, walking and stair climbing. As a practical application, the relative role played by volume and intensity of overall physical activity and selected habitual activities should be taken into account in the design of preventative training interventions to preserve mobility as individuals grow older.
Leisure-time physical activity (PA) has been established to be related to more years lived without disability. However, less is known about the relationship between occupational PA and disability in old age. The aim of the study was 1) to investigate whether midlife occupational PA is related to late-life disability, and 2) to test the hypothesis that the association differs according to the occupational categories of blue and white collar work.
The study population was derived from the Swedish National Study on Aging and Care, and consisted of a random sample of 1804 subjects aged 72 and above. The association of occupational PA during the longest held occupation with disability in old age was determined using logistic regression.
There was no significant relationship between occupational PA and disability in personal or instrumental activities of daily living (ADL) after controlling for demographic and health-related factors. However, in stratified analyses moderate levels of occupational PA was associated with a lower odds ratio of dependency in personal ADL amongst white collar workers, compared to low level of occupational PA (OR = 0.34 95% C1 0.12–0.98).
Moderate levels of midlife occupational PA were associated with a decreased risk of personal ADL disability in old age among white collar workers, but not among blue collar workers. Our results highlight the importance of encouraging white collar workers to engage in physical activity during or outside work hours.
Telomeres are involved in cellular ageing and shorten with increasing age. If telomere length is a valuable biomarker of ageing, then telomere shortening should be associated with worse physical performance, an ageing trait, but evidence for such an association is lacking. The purpose of this study was to examine whether change in telomere length is associated with physical performance.
Using data from four UK adult cohorts (ages 53–80 years at baseline), we undertook cross-sectional and longitudinal analyses. We analysed each study separately and then used meta-analytic methods to pool the results. Physical performance was measured using walking and chair rise speed, standing balance time and grip strength. Telomere length was measured by quantitative real-time polymerase chain reaction (PCR) in whole blood at baseline and follow-up (time 1, time 2).
Total sample sizes in meta-analyses ranged from 1,217 to 3,707. There was little evidence that telomere length was associated with walking speed, balance or grip strength, though weak associations were seen with chair rise speed and grip strength at baseline (p = 0.02 and 0.01 respectively). Faster chair rise speed at follow-up, was associated with a smaller decline in telomere length between time 1 and time 2 (standardised coefficient per SD increase 0.061, 95% CI 0.006, 0.115, p = 0.03) but this was consistent with chance (p = 0.08) after further adjustment.
Whereas shortening of leukocyte telomeres might be an important measure of cellular ageing, there is little evidence that it is a strong biomarker for physical performance.
Both telomere length and mitochondrial function are accepted as reflective indices of aging. Recent studies have shown that telomere dysfunction may influence impaired mitochondrial biogenesis and function. However, there has been no study regarding the possible association between telomere and mitochondrial function in humans. Therefore, the purpose of the study was to identify any relationships between mitochondrial and telomere function.
The present study included 129 community-dwelling, elderly women. The leukocyte mitochondrial DNA copy number and telomere length were measured using a quantitative real-time polymerase chain reaction method. Anthropometric measurement, biochemical blood testing, a depression screening questionnaire using a 15-question geriatric depression scale (GDS-15), and a cognitive function test using the Korean version of the mini mental state examination (K-MMSE) were performed.
Leukocyte mtDNA copy number was positively associated with telomere length (r=0.39, p=<0.0001) and K-MMSE score (r=0.06, p=0.02). Additionally, leukocyte mtDNA copy number was negatively correlated with GDS-15 score (r=-0.17, p=0.04). Age (r=-0.15, p=0.09), waist circumference (r=-0.16, p=0.07), and serum ferritin level (r=-0.13, p=0.07) tended to be inversely correlated with leukocyte mtDNA copy number. With a stepwise multiple regression analysis, telomere length was found to be an independent factor associated with leukocyte mtDNA copy number after adjustment for confounding variables including age, body mass index, waist circumference, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, hs-CRP, serum ferritin, HOMA-IR, K-MMSE, GDS-15, hypertension, diabetes, dyslipidemia, currently smoking, alcohol drinking, and regular exercise.
This study showed that leukocyte mtDNA copy number was positively correlated with leukocyte telomere length in community-dwelling elderly women. Our findings suggest that telomere function may influence mitochondrial function in humans.
Evidence suggests that flavonoid-rich foods are capable of inducing improvements in memory and cognition in animals and humans. However, there is a lack of clarity concerning whether flavonoids are the causal agents in inducing such behavioral responses. Here we show that supplementation with pure anthocyanins or pure flavanols for 6 weeks, at levels similar to that found in blueberry (2% w/w), results in an enhancement of spatial memory in 18 month old rats. Pure flavanols and pure anthocyanins were observed to induce significant improvements in spatial working memory (p = 0.002 and p = 0.006 respectively), to a similar extent to that following blueberry supplementation (p = 0.002). These behavioral changes were paralleled by increases in hippocampal brain-derived neurotrophic factor (R = 0.46, p<0.01), suggesting a common mechanism for the enhancement of memory. However, unlike protein levels of BDNF, the regional enhancement of BDNF mRNA expression in the hippocampus appeared to be predominantly enhanced by anthocyanins. Our data support the claim that flavonoids are likely causal agents in mediating the cognitive effects of flavonoid-rich foods.
Organisational culture is increasingly recognised as important for provision of high-quality long-term care. We undertook this study to measure organisational culture in residential aged care facilities in two Australian states.
Cross-sectional observational study in 21 residential aged care facilities in Western Australia (n = 14) and Queensland (n = 7), Australia. Staff and next-of-kin of residents participated. Measurement comprised surveys of facility staff and residents' next-of-kin, and structured observation of indicators of care quality. Staff tended to rate organisational culture positively. Some qualitative feedback from staff emphasised negative perceptions of communication, leadership and teamwork. Staffing levels were perceived as a dominant challenge, threatening care quality. Direct observation revealed variability within and between facilities but suggested that most facilities (n = 12) were in the typical range, or were quality facilities (n = 8).
There was scope to strengthen organisational culture in participating aged care facilities.
Pramanicin (PMC) is an antifungal agent that was previously demonstrated to exhibit antiangiogenic and anticancer properties in a few in vitro studies. We initially screened a number of PMC analogs for their cytotoxic effects on HCT116 human colon cancer cells. PMC-A, the analog with the most potent antiproliferative effect was chosen to further interrogate the underlying mechanism of action. PMC-A led to apoptosis through activation of caspase-9 and -3. The apoptotic nature of cell death was confirmed by abrogation of cell death with pretreatment with specific caspase inhibitors. Stress-related MAPKs JNK and p38 were both activated concomittantly with the intrinsic apoptotic pathway. Moreover, pharmacological inhibition of p38 proved to attenuate the cell death induction while pretreatment with JNK inhibitor did not exhibit a protective effect. Resistance of Bax −/− cells and the protective nature of caspase-9 inhibition indicate that mitochondria play a central role in PMC-A induced apoptosis. Early post-exposure elevation of cellular Bim and Bax was followed by a marginal Bcl-2 depletion and Bid cleavage. Further analysis revealed that Bcl-2 downregulation occurs at the mRNA level and is critical to mediate PMC-A induced apoptosis, as ectopic Bcl-2 expression substantially spared the cells from death. Conversely, forced expression of Bim proved to significantly increase cell death. In addition, analyses of p53−/− cells demonstrated that Bcl-2/Bim/Bax modulation and MAPK activations take place independently of p53 expression. Taken together, p53-independent transcriptional Bcl-2 downregulation and p38 signaling appear to be the key modulatory events in PMC-A induced apoptosis.
Hydrogen sulfide (H2S) has been shown to have cytoprotective effects in models of hypertension, ischemia/reperfusion and Alzheimer's disease. However, little is known about its effects or mechanisms of action in atherosclerosis. Therefore, in the current study we evaluated the pharmacological effects of H2S on antioxidant defenses and mitochondria protection against hydrogen peroxide (H2O2) induced endothelial cells damage.
Methodology and Principal Findings
H2S, at non-cytotoxic levels, exerts a concentration dependent protective effect in human umbilical vein endothelial cells (HUVECs) exposed to H2O2. Analysis of ATP synthesis, mitochondrial membrane potential (ΔΨm) and cytochrome c release from mitochondria indicated that mitochondrial function was preserved by pretreatment with H2S. In contrast, in H2O2 exposed endothelial cells mitochondria appeared swollen or ruptured. In additional experiments, H2S was also found to preserve the activities and protein expressions levels of the antioxidants enzymes, superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase in H2O2 exposed cells. ROS and lipid peroxidation, as assessed by measuring H2DCFDA, dihydroethidium (DHE), diphenyl-l-pyrenylphosphine (DPPP) and malonaldehyde (MDA) levels, were also inhibited by H2S treatment. Interestingly, in the current model, D, L-propargylglycine (PAG), a selective inhibitor of cystathionine γ-lyase (CSE), abolished the protective effects of H2S donors.
This study is the first to show that H2S can inhibit H2O2 mediated mitochondrial dysfunction in human endothelial cells by preserving antioxidant defences.
H2S may protect against atherosclerosis by preventing H2O2 induced injury to endothelial cells. These effects appear to be mediated via the preservation of mitochondrial function and by reducing the deleterious effects of oxidative stress.
Caloric restriction (CR), a reduction of food intake while avoiding malnutrition, can delay the onset of cancer and age-related diseases in several species, including mice. In addition, depending of the genetic background, CR can also increase or decrease mouse longevity. This has highlighted the importance of identifying the molecular pathways that interplay with CR in modulating longevity. Significant lifespan extension in mice has been recently achieved through over-expression of the catalytic subunit of mouse telomerase (mTERT) in a cancer protective background. Given the CR cancer-protective effects in rodents, we set to address here whether CR impacts on telomere length and synergizes with mTERT to extend mouse longevity. CR significantly decreased tumor incidence in TERT transgenic (TgTERT) mice and extended their lifespan compared to wild-type (WT) controls under the same diet, indicating a synergy between TgTERT and CR in increasing mouse longevity. In addition, longitudinal telomere length measurements in peripheral blood leukocytes from individual mice showed that CR resulted in maintenance and/or elongation telomeres in a percentage of WT mice, a situation that mimics telomere dynamics in TgTERT cohorts. These results demonstrate that CR attenuates telomere erosion associated to aging and that synergizes with TERT over-expression in increasing “health span” and extending mouse longevity.
Previous military studies have shown an energy deficit during a strenuous field training course (TC). This study aimed to determine the effects of energy bar supplementation on energy balance, physical activity (PA), physical performance and well-being and to evaluate ad libitum fluid intake during wintertime 8-day strenuous TC.
Twenty-six men (age 20±1 yr.) were randomly divided into two groups: The control group (n = 12) had traditional field rations and the experimental (Ebar) group (n = 14) field rations plus energy bars of 4.1 MJ•day−1. Energy (EI) and water intake was recorded. Fat-free mass and water loss were measured with deuterium dilution and elimination, respectively. The energy expenditure was calculated using the intake/balance method and energy availability as (EI/estimated basal metabolic rate). PA was monitored using an accelerometer. Physical performance was measured and questionnaires of upper respiratory tract infections (URTI), hunger and mood state were recorded before, during and after TC.
Ebar had a higher EI and energy availability than the controls. However, decreases in body mass and fat mass were similar in both groups representing an energy deficit. No differences were observed between the groups in PA, water balance, URTI symptoms and changes in physical performance and fat-free mass. Ebar felt less hunger after TC than the controls and they had improved positive mood state during the latter part of TC while controls did not. Water deficit associated to higher PA. Furthermore, URTI symptoms and negative mood state associated negatively with energy availability and PA.
An easy-to-use protein-rich energy bars did not prevent energy deficit nor influence PA during an 8-day TC. The high content of protein in the bars might have induced satiation decreasing energy intake from field rations. PA and energy intake seems to be primarily affected by other factors than energy supplementation such as mood state.
Epidemiological data suggest that plant-derived phenolics beneficial effects include an inhibition of LDL oxidation. After applying a screening method based on 2,4-dinitrophenyl hydrazine- protein carbonyl reaction to 21 different plant-derived phenolic acids, we selected the most antioxidant ones. Their effect was assessed in 5 different oxidation systems, as well as in other model proteins. Mass-spectrometry was then used, evidencing a heterogeneous effect on the accumulation of the structurally characterized protein carbonyl glutamic and aminoadipic semialdehydes as well as for malondialdehyde-lysine in LDL apoprotein. After TOF based lipidomics, we identified the most abundant differential lipids in Cu++-incubated LDL as 1-palmitoyllysophosphatidylcholine and 1-stearoyl-sn-glycero-3-phosphocholine. Most of selected phenolic compounds prevented the accumulation of those phospholipids and the cellular impairment induced by oxidized LDL. Finally, to validate these effects in vivo, we evaluated the effect of the intake of a phenolic-enriched extract in plasma protein and lipid modifications in a well-established model of atherosclerosis (diet-induced hypercholesterolemia in hamsters). This showed that a dietary supplement with a phenolic-enriched extract diminished plasma protein oxidative and lipid damage. Globally, these data show structural basis of antioxidant properties of plant-derived phenolic acids in protein oxidation that may be relevant for the health-promoting effects of its dietary intake.
The purpose of this study was to identify the incidence of frailty and to investigate the relationship between frailty status and health-related quality of life (HRQoL) in the community-dwelling elderly population who utilize preventive health services.
People aged 65 years and older who visited a medical center in Taipei City from March to August in 2011 for an annual routine check-up provided by the National Health Insurance were eligible. A total of 374 eligible elderly adults without cognitive impairment had a mean age of 74.6±6.3 years. Frailty status was determined according to the Fried frailty criteria. HRQoL was measured with Short Form-36 (SF-36). Multiple regression analyses examined the relationship between frailty status and the two summary scales of SF-36. Models were adjusted for the participants' sociodemographic and health status.
After adjusting for sociodemographic and health-related covariables, frailty was found to be more significantly associated (p<0.001) with lower scores on both physical and mental health-related quality of life summary scales compared with robustness. For the frailty phenotypes, slowness represented the major contributing factor in the physical component scale of SF-36, and exhaustion was the primary contributing factor in the mental component scale.
The status of frailty is closely associated with HRQoL in elderly Taiwanese preventive health service users. The impacts of frailty phenotypes on physical and mental aspects of HRQoL differ.
Age-associated decline in testosterone levels represent one of the potential mechanisms involved in the development of frailty. Although this association has been widely reported in older men, very few data are available in women. We studied the association between testosterone and frailty in women and assessed sex differences in this relationship.
We used cross-sectional data from the Toledo Study for Healthy Aging, a population-based cohort study of Spanish elderly. Frailty was defined according to Fried's approach. Multivariate odds-ratios (OR) and 95% confidence intervals (CI) associated with total (TT) and free testosterone (FT) levels were estimated using polytomous logistic regression.
In women, there was a U-shaped relationship between FT levels and frailty (p for FT2 = 0.03). In addition, very low levels of FT were observed in women with ≥4 frailty criteria (age-adjusted geometric means = 0.13 versus 0.37 in subjects with <4 components, p = 0.010). The association of FT with frailty appeared confined to obese women (p-value for interaction = 0.05).In men, the risk of frailty levels linearly decreased with testosterone (adjusted OR for frailty = 2.9 (95%CI, 1.6–5.1) and 1.6 (95%CI, 1.0–2.5), for 1 SD decrease in TT and FT, respectively). TT and FT showed association with most of frailty criteria. No interaction was found with BMI.
There is a relationship between circulating levels of FT and frailty in older women. This relation seems to be modulated by BMI. The relevance and the nature of the association of FT levels and frailty are sex-specific, suggesting that different biological mechanisms may be involved.
Preclinical studies strongly suggest that accelerated apoptosis in skeletal myocytes may be involved in the pathogenesis of sarcopenia. However, evidence in humans is sparse. In the present study, we investigated whether apoptotic signaling in the skeletal muscle was associated with indices of muscle mass and function in older persons.
Community-dwelling older adults were categorized into high-functioning (HF) or low-functioning (LF) groups according to their short physical performance battery (SPPB) summary score. Participants underwent an isokinetic knee extensor strength test and 3-dimensional magnetic resonance imaging of the thigh. Vastus lateralis muscle samples were obtained by percutaneous needle biopsy and assayed for the expression of a set of apoptotic signaling proteins. Age, sex, number of comorbid conditions and medications as well as knee extensor strength were not different between groups. HF participants displayed greater thigh muscle volume compared with LF persons. Multivariate partial least squares (PLS) regressions showed significant correlations between caspase-dependent apoptotic signaling proteins and the muscular percentage of thigh volume (R2 = 0.78; Q2 = 0.61) as well as gait speed (R2 = 0.81; Q2 = 0.56). Significant variables in the PLS model of percent muscle volume were active caspase-8, cleaved caspase-3, cytosolic cytochrome c and mitochondrial Bak. The regression model of gait speed was mainly described by cleaved caspase-3 and mitochondrial Bax and Bak. PLS predictive apoptotic variables did not differ between functional groups. No correlation was determined between apoptotic signaling proteins and muscle strength or quality (strength per unit volume).
Data from this exploratory study show for the first time that apoptotic signaling is correlated with indices of muscle mass and function in a cohort of community-dwelling older persons. Future larger-scale studies are needed to corroborate these preliminary findings and determine if down-regulation of apoptotic signaling in skeletal myocytes will provide improvements in the muscle mass and functional status of older persons.
Frailty is a dynamic age-related condition of increased vulnerability characterized by declines across multiple physiologic systems and associated with an increased risk of death. We compared the predictive accuracy for one-month and one-year all-cause mortality of four frailty instruments in a large population of hospitalized older patients in a prospective multicentre cohort study.
Methods and Findings
On 2033 hospitalized patients aged ≥65 years from twenty Italian geriatric units, we calculated the frailty indexes derived from the Study of Osteoporotic Fractures (FI-SOF), based on the cumulative deficits model (FI-CD), based on a comprehensive geriatric assessment (FI-CGA), and the Multidimensional Prognostic Index (MPI). The overall mortality rates were 8.6% after one-month and 24.9% after one-year follow-up. All frailty instruments were significantly associated with one-month and one-year all-cause mortality. The areas under the receiver operating characteristic (ROC) curves estimated from age- and sex-adjusted logistic regression models, accounting for clustering due to centre effect, showed that the MPI had a significant higher discriminatory accuracy than FI-SOF, FI-CD, and FI-CGA after one month (areas under the ROC curves: FI-SOF = 0.685 vs. FI-CD = 0.738 vs. FI-CGA = 0.724 vs. MPI = 0.765, p<0.0001) and one year of follow-up (areas under the ROC curves: FI-SOF = 0.694 vs. FI-CD = 0.729 vs. FI-CGA = 0.727 vs. MPI = 0.750, p<0.0001). The MPI showed a significant higher discriminatory power for predicting one-year mortality also in hospitalized older patients without functional limitations, without cognitive impairment, malnourished, with increased comorbidity, and with a high number of drugs.
All frailty instruments were significantly associated with short- and long-term all-cause mortality, but MPI demonstrated a significant higher predictive power than other frailty instruments in hospitalized older patients.
In humans Uncoupling Proteins (UCPs) are a group of five mitochondrial inner membrane transporters with variable tissue expression, which seem to function as regulators of energy homeostasis and antioxidants. In particular, these proteins uncouple respiration from ATP production, allowing stored energy to be released as heat. Data from experimental models have previously suggested that UCPs may play an important role on aging rate and lifespan. We analyzed the genetic variability of human UCPs in cohorts of subjects ranging between 64 and 105 years of age (for a total of 598 subjects), to determine whether specific UCP variability affects human longevity. Indeed, we found that the genetic variability of UCP2, UCP3 and UCP4 do affect the individual's chances of surviving up to a very old age. This confirms the importance of energy storage, energy use and modulation of ROS production in the aging process. In addition, given the different localization of these UCPs (UCP2 is expressed in various tissues including brain, hearth and adipose tissue, while UCP3 is expressed in muscles and Brown Adipose Tissue and UCP4 is expressed in neuronal cells), our results may suggest that the uncoupling process plays an important role in modulating aging especially in muscular and nervous tissues, which are indeed very responsive to metabolic alterations and are very important in estimating health status and survival in the elderly.
Oxidative stress and mitochondrial function are at the core of many degenerative conditions. However, the interaction between oxidative stress and in vivo mitochondrial function is unclear. We used both pharmacological (2 week paraquat (PQ) treatment of wild type mice) and transgenic (mice lacking Cu, Zn-superoxide dismutase (SOD1−/−)) models to test the effect of oxidative stress on in vivo mitochondrial function in skeletal muscle. Magnetic resonance and optical spectroscopy were used to measure mitochondrial ATP and oxygen fluxes and cell energetic state. In both models of oxidative stress, coupling of oxidative phosphorylation was significantly lower (lower P/O) at rest in vivo in skeletal muscle and was dose-dependent in the PQ model. Despite this reduction in efficiency, in vivo mitochondrial phosphorylation capacity (ATPmax) was maintained in both models, and ex vivo mitochondrial respiration in permeabilized muscle fibers was unchanged following PQ treatment. In association with the reduced P/O, PQ treatment led to a dose-dependent reduction in PCr/ATP ratio and increased phosphorylation of AMPK. These results indicate that oxidative stress uncouples oxidative phosphorylation in vivo and results in energetic stress in the absence of defects in the mitochondrial electron transport chain.
Short telomere length (TL) is an independent predictor of mortality in patients with coronary heart disease (CHD). However, the relationship between physical fitness and TL has not been explored in these patients.
In a cross sectional study of 944 outpatients with stable CHD, we performed exercise treadmill testing, assessed self-reported physical activity, and measured leukocyte TL using a quantitative PCR assay. We used generalized linear models to calculate mean TL (T/S ratio), and logistic regression models to compare the proportion of patients with short TL (defined as the lowest quartile), among participants with low, medium and high physical fitness, based on metabolic equivalent tasks achieved (METs).
229 participants had low physical fitness (<5 METS), 334 had moderate physical fitness (5–7 METS), and 381 had high physical fitness (>7 METS). Mean ± T/S ratio ranged from 0.86±0.21 (5349±3781 base pairs) in those with low physical fitness to 0.95±0.23 (5566±3829 base pairs) in those with high physical fitness (p<.001). This association remained strong after adjustment for numerous patient characteristics, including measures of cardiac disease severity and physical inactivity (p = 0.005). Compared with participants with high physical fitness, those with low physical fitness had 2-fold greater odds of having TL in the lowest quartile (OR 2.39, 95% CI 1.60–3.55; p<.001). This association was similar after multivariable adjustment (OR 1.94, 95%CI, 1.18–3.20; p = 0.009). Self-reported physical inactivity was associated with shorter TL in unadjusted analyses, but not after multivariable adjustment.
We found that worse objectively-assessed physical fitness is associated with shorter leukocyte telomere length in patients with CHD. The clinical implications of this association deserve further study.
Telomere length has been proposed as a marker of aging. However, our knowledge of lifestyle risk factors determining telomere length is limited.
We evaluated the associations between years of rotating night shifts, self-reported sleep duration, and telomere length in 4,117 female participants from the Nurses' Health Study. Telomere length in peripheral blood leukocytes was determined by Real-Time PCR assay. Information on rotating night shifts and sleep duration was collected via questionnaires prior to blood collection. We used multivariable linear regression to investigate the associations between rotating night shifts, sleep duration, and telomere length.
Compared with women in the category (9 hours), those in the lowest category of sleep duration (≤6 hours) had a 0.12 unit decrease in z score after adjustment for age, BMI and cigarette smoking (equivalent to 9-year telomere attrition, P for trend = 0.05). Significant positive association between sleep duration and telomere length was seen among women under age of 50 (P for trend = 0.004), but not among those over 50 (P for trend = 0.33) (P for interaction = 0.005). In addition, we observed that women with a longer history of rotating night shifts tended to have shorter telomere length, but this relation was not statistically significant (P for trend = 0.36).
We found that sleep duration was positively associated with telomere length among women under 50 years old. Further research is needed to confirm the observed associations.
Resveratrol is a natural compound suggested to have beneficial health effects. However, people are consuming resveratrol for this reason without having the adequate scientific evidence for its effects in humans. Therefore, scientific valid recommendations concerning the human intake of resveratrol based on available published scientific data are necessary. Such recommendations were formulated after the Resveratrol 2010 conference, held in September 2010 in Helsingør, Denmark.
Literature search in databases as PubMed and ISI Web of Science in combination with manual search was used to answer the following five questions: 1Can resveratrol be recommended in the prevention or treatment of human diseases?; 2Are there observed “side effects” caused by the intake of resveratrol in humans?; 3What is the relevant dose of resveratrol?; 4What valid data are available regarding an effect in various species of experimental animals?; 5Which relevant (overall) mechanisms of action of resveratrol have been documented?
The overall conclusion is that the published evidence is not sufficiently strong to justify a recommendation for the administration of resveratrol to humans, beyond the dose which can be obtained from dietary sources. On the other hand, animal data are promising in prevention of various cancer types, coronary heart diseases and diabetes which strongly indicate the need for human clinical trials. Finally, we suggest directions for future research in resveratrol regarding its mechanism of action and its safety and toxicology in human subjects.
Accumulated evidences have shown that vascular risk factors, e.g., hypertension, diabetes mellitus and hyperlipidemia, may be related to the risk of dementia. This study investigated the association between genetic polymorphisms of a vascular susceptibility gene, Ninjurin2 (NINJ2), and the risk of dementia, which has not been explored previously.
A total of 275 Alzheimer's disease (AD) patients and 119 vascular dementia (VaD) patients aged 50 or older were recruited from three teaching hospitals from 2007 to 2010. Healthy controls (n = 423) with the same age of cases were recruited from the health checkup and volunteers worked at the hospital during the same time period. Five common (frequency >5%) haplotype-tagging single nucleotide polymorphisms (htSNPs) in NINJ2 were genotyped to test for the association between sequence variants of NINJ2 and dementia risk, and how vascular risk factors modify this association.
Homozygosity of two NINJ2 SNPs was significantly associated with a decreased risk of AD [rs11833579: adjusted odds ratio (AOR) = 0.43; 95% confidence interval (CI) = 0.23–0.80; rs12425791: AOR = 0.33, 95% CI = 0.12–0.96]. Five common haplotypes (cumulative frequency = 97%) were identified. The global test for the association between NINJ2 haplotypes and AD was significant (p = 0.03). Haplotype CAGGA was significantly associated with a decreased risk of AD (AOR = 0.32, 95% CI = 0.11–0.94). No associations were observed for VaD.
Inherited polymorphisms of the vascular susceptibility gene NINJ2 were associated with AD risk.
Type 2 diabetes (T2DM) is a heterogeneous group of diseases that is progressive and involves multiple tissues. Goto-Kakizaki (GK) rats are a polygenic model with elevated blood glucose, peripheral insulin resistance, a non-obese phenotype, and exhibit many degenerative changes observed in human T2DM. As part of a systems analysis of disease progression in this animal model, this study characterized the contribution of adipose tissue to pathophysiology of the disease. We sacrificed subgroups of GK rats and appropriate controls at 4, 8, 12, 16 and 20 weeks of age and carried out a gene array analysis of white adipose tissue. We expanded our physiological analysis of the animals that accompanied our initial gene array study on the livers from these animals. The expanded analysis included adipose tissue weights, HbA1c, additional hormonal profiles, lipid profiles, differential blood cell counts, and food consumption. HbA1c progressively increased in the GK animals. Altered corticosterone, leptin, and adiponectin profiles were also documented in GK animals. Gene array analysis identified 412 genes that were differentially expressed in adipose tissue of GKs relative to controls. The GK animals exhibited an age-specific failure to accumulate body fat despite their relatively higher calorie consumption which was well supported by the altered expression of genes involved in adipogenesis and lipogenesis in the white adipose tissue of these animals, including Fasn, Acly, Kklf9, and Stat3. Systemic inflammation was reflected by chronically elevated white blood cell counts. Furthermore, chronic inflammation in adipose tissue was evident from the differential expression of genes involved in inflammatory responses and activation of natural immunity, including two interferon regulated genes, Ifit and Iipg, as well as MHC class II genes. This study demonstrates an age specific failure to accumulate adipose tissue in the GK rat and the presence of chronic inflammation in adipose tissue from these animals.
There is no consensus regarding the optimal approach to assessment of the quality of life of people with dementia. We undertook the present study to describe and determine the factors associated with ratings of the quality of life of a cohort of people with dementia living in a residential care facility.
351 people with dementia living in residential care facilities, and their staff and family informants participated in this cross sectional observational study. Quality of life was measured using self (Quality of Life in Alzheimer's Disease [QoL-AD] scale), and informant (QoL-AD and Alzheimer's Disease Related QoL Scale) reports. 226 people (64%) with dementia (median MMSE 17; 12–21) were able to self rate the QoL-AD scale and these subjects' ratings were compared to ratings by staff and family. Both staff and family informant ratings of the QoL-AD underestimated self ratings (mean difference −7.8, 95% CI −8.8, −6.7 for staff rated QoL-AD; and mean difference −7.2, 95% CI −8.5, −6.0 for family rated QoL-AD). Self ratings of QoL were lower among people who were restrained, had fallen or had pain. Informant ratings of the QoL of the participants with dementia were consistently and significantly lower for people with severe cognitive impairment, who had fallen, had presence of neuropsychiatric symptoms, or where care giver distress was present. Documented restraint, reported pain and neuropsychiatric symptoms were independently associated with lower self rating of the QoL-AD in multivariate models. Cognitive impairment, case conferencing, hospitalizations and neuropsychiatric symptoms were found to be independently associated with staff rated ADRQL.
The majority of people with dementia living in residential care facilities can rate their own QoL. Informant ratings underestimate self ratings of QoL of people with dementia, and appear to be associated with factors which are not associated with self ratings.
Impaired expression of selenium-containing proteins leads to perturbed thyroid hormone (TH) levels, indicating the central importance of selenium for TH homeostasis. Moreover, critically ill patients with declining serum selenium develop a syndrome of low circulating TH and a central downregulation of the hypothalamus-pituitary-thyroid axis. This prompted us to test the reciprocal effect, i.e., if TH status would also regulate selenoprotein expression and selenium levels. To investigate the TH dependency of selenium metabolism, we analyzed mice expressing a mutant TH receptor α1 (TRα1+m) that confers a receptor-mediated hypothyroidism. Serum selenium was reduced in these animals, which was a direct consequence of the mutant TRα1 and not related to their metabolic alterations. Accordingly, hyperthyroidism, genetically caused by the inactivation of TRβ or by oral TH treatment of adult mice, increased serum selenium levels in TRα1+m and controls, thus demonstrating a novel and specific role for TRα1 in selenium metabolism. Furthermore, TH affected the mRNA levels for several enzymes involved in selenoprotein biosynthesis as well as serum selenoprotein P concentrations and the expression of other antioxidative selenoproteins. Taken together, our results show that TH positively affects the serum selenium status and regulates the expression of several selenoproteins. This demonstrates that selenium and TH metabolism are interconnected through a feed-forward regulation, which can in part explain the rapid parallel downregulation of both systems in critical illness.
Chronic psychological stress is associated with detrimental effects on physical health, and may operate in part through accelerated cell aging, as indexed by shorter telomeres at the ends of chromosomes. However, not all people under stress have distinctly short telomeres, and we examined whether exercise can serve a stress-buffering function. We predicted that chronic stress would be related to short telomere length (TL) in sedentary individuals, whereas in those who exercise, stress would not have measurable effects on telomere shortening.
Methodology and Principal Findings
63 healthy post-menopausal women underwent a fasting morning blood draw for whole blood TL analysis by a quantitative polymerase chain reaction method. Participants completed the Perceived Stress Scale (Cohen et al., 1983), and for three successive days reported daily minutes of vigorous activity. Participants were categorized into two groups-sedentary and active (those getting Centers for Disease Control-recommended daily amount of activity). The likelihood of having short versus long telomeres was calculated as a function of stress and exercise group, covarying age, BMI and education. Logistic regression analyses revealed a significant moderating effect of exercise. As predicted, among non-exercisers a one unit increase in the Perceived Stress Scale was related to a 15-fold increase in the odds of having short telomeres (p<.05), whereas in exercisers, perceived stress appears to be unrelated to TL (B = −.59, SE = .78, p = .45).
Vigorous physical activity appears to protect those experiencing high stress by buffering its relationship with TL. We propose pathways through which physical activity acts to buffer stress effects.