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Fat oxidation decreases with age, yet no studies have previously investigated if aging affects the maximal fat oxidation rate (MFO) during exercise in men and women differently. We hypothesized that increased age would be associated with a decline in MFO and this would be more pronounced in women due to menopause, compared with men. In this cross-sectional study design, 435 (247/188, male/female) subjects of varying ages performed a DXA scan, a submaximal graded exercise test and a maximal oxygen uptake test, to measure MFO and cardiorespiratory fitness (CRF) by indirect calorimetry. Subjects were stratified into 12 groups according to sex (male/female), age (<45, 45–55 and >55 years), CRF (below average and above average). Women aged <45 years had a higher MFO relative to fat free mass (FFM) (mg/min/kg) compared with men, regardless of CRF. However, there were no differences in MFO (mg/min/kg FFM) between men and women, in the groups aged between 45–55 and >55 years. In summary, we found that women aged <45 years display a higher MFO (mg/min/kg FFM) compared with men and that this sexual divergence is abolished after the age of 45 years. Novelty: Maximal fat oxidation rate is higher in young women compared with men. This sex-related difference is attenuated after the age of 45 years. Cardiorespiratory fitness does not influence this sex-related difference. [ABSTRACT FROM AUTHOR]

Short telomere length (TL) is associated with atherosclerotic cardiovascular disease (ACVD) and other age-related diseases. It is unclear whether these associations originate from having inherently short TL or a faster TL attrition before or during disease development. We proposed the blood-and-muscle model to assess TL dynamics throughout life course. Our objective was to measure TL in leukocytes (LTL) and in skeletal muscle (MTL), which served as a proxy of TL at birth. The delta (MTL–LTL) represented life-long telomere attrition. Blood draws and skeletal muscle biopsies were performed on 35 Lebanese individuals undergoing surgery. Following DNA extraction, LTL and MTL were measured by Southern blot. In every individual aged between 30 and 85 years, MTL was longer than LTL. With age, MTL and LTL decreased, but the delta (MTL–LTL) increased by 14 bp/year. We validated the blood-and-muscle model that allowed us to identify TL, TL at birth, and lifelong TL attrition in a cross-sectional study. This model can be used in larger cross-sectional studies to evaluate the association of telomere dynamics with age-related diseases onset and progression. [ABSTRACT FROM AUTHOR]

Immunosenescence contribute to increase the blood-brain barrier (BBB) permeability, leading cognitive impairment and neurodegeneration. Thus, we investigated the anti-inflammatory effect of exercise and taurine supplementation on peripheral markers of BBB, inflammation, and cognition of elderly women. Forty-eight elderly women (age, 83.58 ± 6.9 years) participated in the study, and were allocated into combined exercise training (CET: n = 13), taurine supplementation (TAU: n = 12), exercise training associated with taurine (CET+TAU: n = 11), or control (CG: n = 12) groups. Exercise was applied twice a week (multi-modal exercise). Taurine ingestion was 1.5 g., once a day. Participants were evaluated before and after 14-weeks of intervention. Plasma levels of interleukin (IL)-1β, IL-1ra, IL-6, IL-10, IL-17, tumor necrosis factor alpha (TNF-α), and serum concentration of S100β and neuron specific enolase (NSE) were determined. The mini mental state examination (MMSE) was also applied. Concentrations of S100β were maintained in all intervention groups, while a subtle increase in the CG was found. NSE levels increased only in TAU group ( p < 0.05). CET reduced TNF-α, IL-6, and IL-1β/IL-1ra, IL-6/IL10, and TNF-α/IL-10 ratios ( p < 0.05). TAU decreased the IL-1β/IL-1ra ratio ( p < 0.05). MMSE score increased only in the CET+TAU group ( p < 0.05). Multiple regression analysis showed that there was a trend for changes in IL-1β and the Charlson Comorbidity Index to be independently associated with changes in S100β. Exercise and taurine decreased inflammation, and maintained the BBB integrity in elderly women. Exercise emerged as an important tool to improve brain health even when started at advanced ages. [ABSTRACT FROM AUTHOR]

The aim of the present study was to compare muscular performance and body composition changes following low-volume resistance-training programs consisting of multi-joint (MJ) exercises (cable chest press and seated row) versus a combination of multi- and single-joint (MJ+SJ) exercises (cable chest press, seated row, biceps curl, and triceps extension). Thirty untrained healthy aging adults were randomly assigned to 3 groups: MJ ( n = 11), MJ+SJ ( n = 11), and control ( n = 8). Twelve-repetition maximums (12-RMs) for the cable chest press and seated row, localized muscular endurance for the elbow flexors handgrip strength, and body composition were assessed before and after the 8-week training program. All comparisons were analyzed via a mixed-model analysis with repeated measures (group × time) and the Bonferroni post hoc test ( p < 0.05). The MJ and MJ+SJ groups increased performance in the 12-RM cable chest press (MJ = 61.5% ± 24.6% and MJ+SJ = 71.1% ± 25.6%), 12-RM seated row (MJ = 46.4% ± 26.3% and MJ+SJ = 51.5% ± 21.0%), localized muscular endurance (MJ = 24.7% ± 16.7% and MJ+SJ = 37.0% ± 11.4%), and handgrip strength (MJ = 9.3% ± 10.4% and MJ+SJ = 16.6% ± 25.3%) after the intervention. Body composition (i.e., trunk and upper limb fat and lean mass) did not change for any groups. No significant differences were observed between the MJ versus the MJ+SJ protocols after the intervention for any variables. In conclusion, for aging adults, either MJ or MJ+SJ low-volume resistance training resulted in similar increases in 12-RM, localized muscular endurance, and handgrip strength, without changes in body composition after 8 weeks of training. [ABSTRACT FROM AUTHOR]

Physical activity screening prior to starting a physical activity program is important to identify if there are any underlying health conditions. However, many older adults do not complete such assessments prior to beginning their physical activity program. This project compared the Canadian Society for Exercise Physiology's newly developed Get Active Questionnaire (GAQ) to a standardized exercise stress test in terms of screening out versus screening in false-positive GAQ tests. A convenience sample of community-dwelling adults (male n = 58, female n = 54) aged 75 ± 7 years from London, Ontario, Canada, was used. Participants completed a physical exam and physical activity screening session (i.e., stress test and GAQ) at a research laboratory that routinely conducts community-based referrals. One week after the initial visit, participants returned to the study site, completed the GAQ, and were asked questions about their perceptions of physical activity screening by a research assistant. The GAQ 'screened in' participants, but it did not provide the same precision of 'screening out' at-risk individuals as an exercise stress test; the GAQ reduced false-positives versus the stress test, yet there was a large proportion of high false-negative results reported. The GAQ shows promise in physical activity screening in older adults to engage in exercise safely. However, the lack of precision in physical-activity screening out of at-risk populations requires further evaluation. Questionnaires such as the GAQ should be evaluated in a larger study population at various time points to further assess the validity and reliability of physical activity screening tools. [ABSTRACT FROM AUTHOR]

Whey protein concentrate (WPC) is a rich source of sulfur-containing amino acids and is consumed as a functional food, incorporating a wide range of nutritional attributes. The purpose of this study is to evaluate the neuroprotective effect of WPC on rat brain during aging. Young (4 months) and old (24 months) male Wistar rats were supplemented with WPC (300 mg/kg body weight) for 28 days. Biomarkers of oxidative stress and antioxidant capacity in terms of ferric reducing antioxidant potential (FRAP), lipid hydroperoxide (LHP), total thiol (T-SH), protein carbonyl (PC), reactive oxygen species (ROS), nitric oxide (NO), and acetylcholinesterase (AChE) activity were measured in brain of control and experimental (WPC supplemented) groups. In addition, gene expression and histopathological studies were also performed. The results indicate that WPC augmented the level of FRAP, T-SH, and AChE in old rats as compared with the old control. Furthermore, WPC-treated groups exhibited significant reduction in LHP, PC, ROS, and NO levels in aged rats. WPC supplementation also downregulated the expression of inflammatory markers (tumor necrosis factor alpha, interleukin (IL)-1β, IL-6), and upregulated the expression of marker genes associated with autophagy (Atg3, Beclin-1, LC3B) and neurodegeneration (neuron specific enolase, Synapsin-I, MBP-2). The findings suggested WPC to be a potential functional nutritional food supplement that prevents the progression of age-related oxidative damage in Wistar rats. [ABSTRACT FROM AUTHOR]

Development of late-onset respiratory diseases is associated with elevated 8-isoprostane, a marker of oxidative stress, in the airways. However, sex differences exist in development of these diseases. Using an exhaustive exercise bout as a physiological stressor may elucidate whether there is a sex difference with aging in pre- to postexercise airway 8-isoprostane generation. The purpose of this study was to determine whether older women exhibit a greater airway 8-isoprostane response to exhaustive exercise compared with older men and younger controls. Thirty-six individuals completed the study (12 postmenopausal older women (OW) and 12 age-matched older men (OM), 65 ± 4 years of age; and 12 younger controls (YC), 21 ± 2 years of age). Baseline measurements included exhaled breath condensate (EBC) for assessment of airway 8-isoprostane and standard pulmonary function tests (PFTs) to assess forced expiratory volume in 1-s (FEV1), forced vital capacity (FVC), FEV1/FVC, and forced expiratory flow at 25%-75% of FVC. Subjects then performed a peak oxygen uptake test to exhaustion on a cycle ergometer. Immediately postexercise, PFTs and EBC were performed. The generation of airway 8-isoprostane from pre- to postexercise was greater in OW compared with OM and YC ( p < 0.01), increasing ∼74% ± 77% in OW, while decreasing in OM (∼12% ± 50%) and YC (∼20.9% ± 30%). The OW exhibited a greater airway 8-isoprostane response to exhaustive exercise compared with OM and YC, which may suggest that sex differences in oxidative stress generation following exhaustive exercise may provide a mechanistic rationale for sex differences in late-onset respiratory diseases. [ABSTRACT FROM AUTHOR]

Aging skeletal muscle displays an altered iron status that may promote oxidative stress and sarcopenia. A diet containing low iron (LI) could reduce muscle iron status and attenuate age-related muscle atrophy. Supplemental branched-chain amino acids (BCAA) may also alleviate sarcopenia by promoting muscle protein synthesis and iron status improvement. This study examined individual and combined effects of LI and BCAA diets on anabolic signaling and iron status in skeletal muscle of aging rats. Twenty-nine-month-old male Fisher 344 × Brown Norway rats consumed the following control-base diets: control + regular iron (35 mg iron/kg) (CR; n = 11); control + LI (∼6 mg iron/kg) (CL; n = 11); 2×BCAA + regular iron (BR; n = 10); and 2×BCAA + LI (BL; n = 12) for 12 weeks. Although LI and/or 2×BCAA did not affect plantaris muscle mass, 2×BCAA groups showed lower muscle iron content than did CR and CL groups ( P < 0.05). p70 ribosomal protein S6 kinase phosphorylation was greater in 2×BCAA and LI animals compared with CR animals ( P < 0.05). Interactions between IRON and BCAA were observed for proteins indicative of mitochondrial biogenesis (peroxisome proliferator-activated receptor gamma coactivator 1 alpha) and oxidative capacity (cytochrome c oxidase subunit 2 and citrate synthase) ( P < 0.05) wherein the combined diet (BL) negated potential benefits of individual diets. Antioxidant capacity, superoxide dismutase activity, and oxidative injury (3-nitrotyrosine, protein carbonyls, and 4-hydroxynonenal) were similar between groups. In conclusion, 12 weeks of LI and 2×BCAA diets showed significant impacts on increasing anabolic signaling as well as ameliorating iron status; however, these interventions did not affect muscle mass. [ABSTRACT FROM AUTHOR]

Erectile dysfunction (ED) has been reported to be associated with inflammation. This study investigated the effects of tumor necrosis factor alpha (TNF-α) inhibitor etanercept on penile neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) expressions, testosterone concentrations, neurogenic and endothelium-dependent relaxations of corpus cavernosum (CC), and circulating and cavernosal levels of inflammatory markers in aged rats. Animals were separated into control, aged, and etanercept-treated aged groups. Aged rats displayed significantly increased serum and cavernosal TNF-α, C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule (ICAM-1) levels, and decreased penile nNOS and eNOS expressions and serum testosterone levels compared with controls. In etanercept-treated aged group, NOS expressions were similar to that of the control group. The circulating and cavernosal concentrations of TNF-α, CRP, MCP-1, ICAM-1, and testosterone were also normalized by etanercept. Neurogenic and endothelium-dependent relaxant responses significantly decreased in aged rats and etanercept treatment markedly improved these relaxation responses. Our findings indicate that aging decreases penile NOS expression, neurogenic and endothelium-dependent relaxations of CC, and also suppresses serum testosterone levels by inducing inflammatory response that may contribute to the development of ED. TNF-α antagonism may be a novel strategy to treat aging-associated ED. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effect of exercise and nitric oxide synthase (NOS) inhibition on memory, anxiety, and protein levels of brain-derived neurotrophic factor (BDNF) and P70S6 kinase (P70S6K). Twenty-month-old rats were divided into 6 groups: a control group, 2 groups treated with l-nitro-arginine methyl ester (L-NAME) (25 or 100 mg/kg) for 63 days, 2 groups treated with L-NAME (25 or 100 mg/kg) for 63 days plus 2 months of exercise, and 1 group treated with exercise. Behavioral tests were conducted to determine the anxiolytic and memory-improving role of exercise and NOS inhibition. BDNF, P70S6K, and cleaved caspase-3 protein levels in the hippocampus and prefrontal cortex were evaluated by Western blotting. Exercise and L-NAME (25 mg/kg) or their combination had an anxiolytic effect and improved spatial memory in old rats compared with the control or exercised group, respectively. Exercise and treatment with a low dose of L-NAME (25 mg/kg) each increased BDNF and P70S6K in the hippocampus and prefrontal cortex compared with levels in control rats. In comparison with exercise alone, co-treatment with exercise and a low dose of L-NAME (25 mg/kg) also increased BDNF and P70S6K in the hippocampus. The neuronal level of cleaved caspase-3 was reduced in the L-NAME (25 mg/kg) + exercise group compared with the exercised group. The L-NAME (100 mg/kg) + exercise treatment had no positive behavioral or molecular effects compared with exercise alone. The protective role of NOS inhibition and aerobic exercise against aging is probably modulated via BDNF and P70S6K in the brain. [ABSTRACT FROM AUTHOR]

Diet composition influences acid-base status of the body. This may become more relevant as renal functional capacity declines with aging. We examined the effects of low (LD) versus high dietary acid load (HD) on blood acid-base status and exercise performance. Participants included 22 adolescents, 33 young adults (YA), and 33 elderly (EL), who followed a 7-day LD and HD in a randomized order. At the end of both diet periods the subjects performed a cycle ergometer test (3 × 10 min at 35%, 55%, 75%, and (except EL) until exhaustion at 100% of maximal oxygen uptake). At the beginning of and after the diet periods, blood samples were collected at rest and after all workloads. Oxygen uptake, respiratory exchange ratio (RER), and heart rate (HR) were monitored during cycling. In YA and EL, bicarbonate (HCO3−) and base excess (BE) decreased over the HD period, and HCO3−, BE, and pH were lower at rest after HD compared with LD. In YA and EL women, HCO3− and BE were lower at submaximal workloads after HD compared with LD. In YA women, the maximal workload was 19% shorter and maximal oxygen uptake, RER, and HR were lower after HD compared with LD. Our data uniquely suggests that better renal function is associated with higher availability of bases, which may diminish exercise-induced acidosis and improve maximal aerobic performance. Differences in glomerular filtration rate between the subject groups likely explains the larger effects of dietary acid load in the elderly compared with younger subjects and in women compared with men. [ABSTRACT FROM AUTHOR]

We evaluated the extent to which age, cardiorespiratory fitness, and body fat can independently determine whole-body heat loss (WBHL) in 87 otherwise healthy adults. We show that increasing age is a major predictor for decreasing WBHL in otherwise healthy adults (aged 20-70 years), accounting for 40% of the variation in the largest study to date. While greater body fat also had a minor detrimental impact on WBHL, there was no significant role for cardiorespiratory fitness. [ABSTRACT FROM AUTHOR]

Frailty is considered a state of high vulnerability for adverse health outcomes for people of the same age. Those who are frail have higher mortality, worse health outcomes, and use more health care services than those who are not frail. Despite this, little is known about the biology of frailty, the effect of frailty on pharmacological or surgical outcomes, and potential interventions to attenuate frailty. In humans, frailty can be quantified using a frailty index (FI) based on the principle of deficit accumulation. The recent development of an FI in naturally ageing mice provides an opportunity to conduct frailty research in a validated preclinical model. The mouse FI has been successfully used across a wide range of applications; however, there are some factors that should be considered in implementing this tool. This review summarises the current literature, presents some original data, and suggests areas for future research on the current applications of the mouse FI, inter-rater reliability of the FI, the effect of observer characteristics and environmental factors on mouse FI scores, and the individual items that make up the FI assessment. The implementation of this tool into preclinical frailty research should greatly accelerate translational research in this important field. [ABSTRACT FROM AUTHOR]

In the vascular system, ageing is accompanied by the accrual of senescent cells and is associated with an increased risk of vascular disease. Endothelial cell (EC) dysfunction is a hallmark of vascular disease and is characterized by decreased angiogenic potential, reduced nitric oxide bioavailability, impaired vasodilation, increased production of ROS, and enhanced inflammation. In ECs, the major producer of nitric oxide is the endothelial nitric oxide synthase (eNOS) enzyme that is encoded by the NOS3 gene. NOS3/eNOS function is tightly regulated at both the transcriptional and post-transcriptional levels to maintain normal vascular function. A key transcriptional regulator of eNOS expression is p53, which has been shown to play a central role in mediating cellular senescence and thereby vascular dysfunction. Herein, we show that, in ECs, the MEOX homeodomain transcription factors decrease the expression of genes involved in angiogenesis, repress eNOS expression at the mRNA and protein levels, and increase the expression of p53. These findings support a role for the MEOX proteins in promoting endothelial dysfunction. [ABSTRACT FROM AUTHOR]

Pharmacological interventions to increase the concentration of high-density lipoprotein (HDL) have led to disappointing results and have contributed to the emergence of the concept of HDL functionality. The anti-atherogenic activity of HDLs can be explained by their functionality or quality. The capacity of HDLs to maintain cellular cholesterol homeostasis and to transport cholesterol from peripheral cells to the liver for elimination is one of their principal anti-atherogenic activities. However, HDLs possess several other attributes that contribute to their protective effect against cardiovascular diseases. HDL functionality is regulated by various proteins and lipids making up HDL particles. However, several studies investigated the role of paraoxonase 1 (PON1) and suggest a significant role of this protein in the regulation of the functionality of HDLs. Moreover, research on PON1 attracted much interest following several studies indicating that it is involved in cardiovascular protection. However, the mechanisms by which PON1 exerts these effects remain to be elucidated. [ABSTRACT FROM AUTHOR]

Reverse cholesterol transport (RCT), which is intimately linked to high-density lipoproteins (HDLs), plays a key role in cholesterol homeostasis and the prevention of atherosclerosis. The goal of the present study was to investigate the effect of aging and advanced glycation end products (AGEs) on RCT as well as on other factors that may affect the antiatherogenic property of HDLs. The transfer of macrophage-derived cholesterol to the plasma and liver and then to the feces for elimination was significantly lower in aged mice than in young mice. Chronic injection of d -galactose (D-gal) or AGEs also significantly reduced RCT (65.3% reduction in [3H]cholesterol levels in the plasma of D-gal-treated mice after 48 h compared with control mice, P < 0.01). The injection of both D-gal and aminoguanidine hydrochloride increased [3H]cholesterol levels in the plasma, although the levels were lower than those of control mice. The in vitro incubation of HDLs with dicarbonyl compounds increased the carbonyl and conjugated diene content of HDLs and significantly reduced PON1 paraoxonase activity (87.4% lower than control HDLs, P < 0.0001). Treating J774A.1 macrophages with glycated fetal bovine serum increased carbonyl formation (39.5% increase, P < 0.003) and reduced ABCA1 protein expression and the capacity of macrophages to liberate cholesterol (69.1% decrease, P < 0.0001). Our results showed, for the first time, that RCT is altered with aging and that AGEs contribute significantly to this alteration. [ABSTRACT FROM AUTHOR]

Blueberries are rich in flavonoids, which possess antioxidant and anti-inflammatory properties. High flavonoid intakes attenuate age-related cognitive decline, but data from human intervention studies are sparse. We investigated whether 12 weeks of blueberry concentrate supplementation improved brain perfusion, task-related activation, and cognitive function in healthy older adults. Participants were randomised to consume either 30 mL blueberry concentrate providing 387 mg anthocyanidins (5 female, 7 male; age 67.5 ± 3.0 y; body mass index, 25.9 ± 3.3 kg·m−2) or isoenergetic placebo (8 female, 6 male; age 69.0 ± 3.3 y; body mass index, 27.1 ± 4.0 kg·m−2). Pre- and postsupplementation, participants undertook a battery of cognitive function tests and a numerical Stroop test within a 1.5T magnetic resonance imaging scanner while functional magnetic resonance images were continuously acquired. Quantitative resting brain perfusion was determined using an arterial spin labelling technique, and blood biomarkers of inflammation and oxidative stress were measured. Significant increases in brain activity were observed in response to blueberry supplementation relative to the placebo group within Brodmann areas 4/6/10/21/40/44/45, precuneus, anterior cingulate, and insula/thalamus ( p < 0.001) as well as significant improvements in grey matter perfusion in the parietal (5.0 ± 1.8 vs -2.9 ± 2.4%, p = 0.013) and occipital (8.0 ± 2.6 vs -0.7 ± 3.2%, p = 0.031) lobes. There was also evidence suggesting improvement in working memory (2-back test) after blueberry versus placebo supplementation ( p = 0.05). Supplementation with an anthocyanin-rich blueberry concentrate improved brain perfusion and activation in brain areas associated with cognitive function in healthy older adults. [ABSTRACT FROM AUTHOR]

Aging is an inevitable biological event that is associated with immune alterations. These alterations are related to increased cellular oxidative stress and micronutrient deficiency. Antioxidant supplementation could improve these age-related abnormalities. The aim of this study was to determine in vitro effects of vitamin A, vitamin C, vitamin E, and nicotinamide adenine dinucleotide (NADH) on T cell proliferation, cytokine release, and cell redox status in the elderly compared with young adults. Peripheral blood lymphocytes were isolated using a density gradient of Histopaque. They were cultured in vitro and stimulated with concanavalin A in the presence or absence of vitamins. Cell proliferation was determined by conducting MTT assays, and based on interleukin-2 and interleukin-4 secretions. Cell oxidant/antioxidant balance was assessed by assaying reduced glutathione (GSH), malondialdehyde, carbonyl protein levels, and catalase activity. The present study demonstrated that T-lymphocyte proliferation was decreased with aging and was associated with cytokine secretion alterations, GSH depletion, and intracellular oxidative stress. In the elderly, vitamin C, vitamin E, and NADH significantly improved lymphocyte proliferation and mitigated cellular oxidative stress, whereas vitamin A did not affect cell proliferation or cell redox status. In conclusion, vitamin C, vitamin E, and NADH supplementation improved T-lymphocytes response in the elderly, and could contribute to the prevention of age-related immune alterations. Consumption of food items containing these vitamins is recommended, and further investigation is necessary to evaluate the effect of vitamin supplementation in vivo. [ABSTRACT FROM AUTHOR]

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We have previously shown that a diet containing epigallocatechin gallate (EGCG) and beta-alanine is not effective in improving either cognitive or muscle function in aged (18 month) mice (Gibbons et al., Behav. Brain Res., 2014, 272:131-140; Pence et al., Appl. Physiol. Nutr. Metab., 2016, 41(2): 181-190). However, this diet reduced oxidative stress in the brain, and previous studies using longer term interventions and other doses have documented beneficial effects in cognitive and muscle function, especially with EGCG. Here we hypothesized that a different dose of EGCG or longer feeding period would be more efficacious in improving cognition. Aged (21-25 mo) Balb/cByJ male mice underwent 63 days of feeding with EGCG at 0, 0.091, or 3.67 mg/g AIN-93M diet and were then subjected to a battery of cognitive and muscle function tests. EGCG feeding at either of the 2 doses did not alter preference for novel versus familiar arm in the Y-maze test ( p = 0.29) and did not affect learning in the active avoidance test ( p = 0.76). Similarly, EGCG did not affect preference for novel versus familiar mice in a social discrimination test ( p = 0.17). Likewise, there was no effect of EGCG on muscle function by grip strength ( p = 0.16), rotarod ( p = 0.18), or treadmill test to exhaustion ( p = 0.25). EGCG reduced mortality in a dose-dependent fashion ( p = 0.05, log-rank test for trend), with 91% of high EGCG, 72% of low EGCG, and 55% of control mice surviving to the end of the study. In conclusion, EGCG improves survival in aged mice but does not affect cognitive or muscle function. [ABSTRACT FROM AUTHOR]

Mutations in High temperature requirement A2 (HtrA2), also designated PARK13, which lead to the loss of its protease activity, have been associated with Parkinson's disease (PD). HtrA2 is a mitochondrial protease that translocates to the cytosol upon the initiation of apoptosis where it participates in the abrogation of inhibitors of apoptosis (IAP) inhibition of caspases. Here, we demonstrate that the loss of the HtrA2 function in the dopaminergic neurons of Drosophila melanogaster results in PD-like phenotypes, and we attempt to restore the age-dependent loss in locomotor ability by co-expressing the sole pro-survival Bcl-2 homologue Buffy. The inhibition of HtrA2 in the dopaminergic neurons of Drosophila resulted in shortened lifespan and impaired climbing ability, and the overexpression of Buffy rescued the reduction in lifespan and the age-dependent loss of locomotor ability. In supportive experiments, the inhibition of HtrA2 in the Drosophila eye results in eye defects, marked by reduction in ommatidia number and increased disruption of the ommatidial array; phenotypes that are suppressed by the overexpression of Buffy. [ABSTRACT FROM AUTHOR]

Hypothalamic inflammation and increased oxidative stress are believed to be mechanisms that contribute to obesity. 4-Hydroxy-2,2,6,6-tetramethylpiperidine- N-oxyl (tempol), a free radical scavenger, has been shown to reduce inflammation and oxidative stress. We hypothesized that brain infusion of tempol would reduce oxidative stress, and thus would reduce food intake and body weight and improve body composition in rats with age-related obesity and known elevated oxidative stress. Furthermore, we predicted an associated increase in markers of leptin signalling, including the silent mating type information regulator 2 homolog 1 (SIRT1)/5′AMP-activated protein kinase (AMPK) pathway and the signal transducer and activator of transcription 3 (STAT3) pathway. For this purpose, osmotic minipumps were placed in the intracerebroventricular region of young (3 months) and aged (23 months) male Fischer 344 x Brown Norway rats for the continuous infusion of tempol or vehicle for 2 weeks. Tempol significantly decreased ( p < 0.01) nicotinamide adenine dinucleotide phosphate oxidase activity in the hypothalamus but failed to reduce food intake or weight gain and did not alter body composition. SIRT1 activity and Acetyl p53 were decreased and phosphorylation of AMPK was increased with age, but they were unchanged with tempol. Basal phosphorylation of STAT3 was unchanged with age or tempol. These results indicate that tempol decreases oxidative stress but fails to alter feeding behaviour, body weight, or body composition. Moreover, tempol does not modulate the SIRT1/AMPK/p53 pathway and does not change leptin signalling. Thus, a reduction in hypothalamic oxidative stress is not sufficient to reverse age-related obesity. [ABSTRACT FROM AUTHOR]

Despite intensive efforts to understand the extent to which skeletal muscle mitochondrial capacity changes in older humans, the answer to this important question remains unclear. To determine what the preponderance of evidence from in vivo studies suggests, we conducted a systematic review and meta-analysis of the effects of age on muscle oxidative capacity as measured noninvasively by magnetic resonance spectroscopy. A secondary aim was to examine potential moderators contributing to differences in results across studies, including muscle group, physical activity status, and sex. Candidate papers were identified from PubMed searches ( n = 3561 papers) and the reference lists of relevant papers. Standardized effects (Hedges' g) were calculated for age and each moderator using data from the 22 studies that met the inclusion criteria ( n = 28 effects). Effects were coded as positive when older (age, ≥55 years) adults had higher muscle oxidative capacity than younger (age, 20-45 years) adults. The overall effect of age on oxidative capacity was positive ( g = 0.171, p < 0.001), indicating modestly greater oxidative capacity in old. Notably, there was significant heterogeneity in this result ( Q = 245.8, p < 0.001; I2 = ∼70%-90%). Muscle group, physical activity, and sex were all significant moderators of oxidative capacity ( p ≤ 0.029). This analysis indicates that the current body of literature does not support a de facto decrease of in vivo muscle oxidative capacity in old age. The heterogeneity of study results and identification of significant moderators provide clarity regarding apparent discrepancies in the literature, and indicate the importance of accounting for these variables when examining purported age-related differences in muscle oxidative capacity. [ABSTRACT FROM AUTHOR]

Frailty is a clinical geriatric syndrome caused by physiological deficits across multiple systems. These deficits make it challenging to sustain homeostasis required for the demands of everyday life. Exercise is likely the best therapy to reverse frailty status. Literature to date suggests that pre-frail older adults, those with 1-2 deficits on the Cardiovascular Health Study-Frailty Phenotype (CHS-frailty phenotype), should exercise 2-3 times a week, for 45-60 min. Aerobic, resistance, flexibility, and balance training components should be incorporated but resistance and balance activities should be emphasized. On the other hand, frail (CHS -frailty phenotype ≥ 3 physical deficits) older adults should exercise 3 times per week, for 30-45 min for each session with an emphasis on aerobic training. During aerobic, balance, and flexibility training, both frail and pre-frail older adults should work at an intensity equivalent to a rating of perceived exertion of 3-4 ('somewhat hard') on the Borg CR10 scale. Resistance-training intensity should be based on a percentage of 1-repetition estimated maximum (1RM). Program onset should occur at 55% of 1RM (endurance) and progress to higher intensities of 80% of 1RM (strength) to maximize functional gains. Exercise is the medicine to reverse or mitigate frailty, preserve quality of life, and restore independent functioning in older adults at risk of frailty. [ABSTRACT FROM AUTHOR]

The proportion of older workers has increased substantially in recent years, with over 25% of the Canadian labour force aged ≥55 years. Along with chronological age comes age-related declines in functional capacity associated with impairments to the cardiorespiratory and muscular systems. As a result, older workers are reported to exhibit reductions in work output and in the ability to perform and/or sustain the required effort when performing work tasks. However, research has presented some conflicting views on the consequences of aging in the workforce, as physically demanding occupations can be associated with improved or maintained physical function. Furthermore, the current methods for evaluating physical function in older workers often lack specificity and relevance to the actual work tasks, leading to an underestimation of physical capacity in the older worker. Nevertheless, industry often lacks the appropriate information and/or tools to accommodate the aging workforce, particularly in the context of physical employment standards. Ultimately, if appropriate workplace strategies and work performance standards are adopted to optimize the strengths and protect against the vulnerability of the aging workers, they can perform as effectively as their younger counterparts. Our aim in this review is to evaluate the impact of different individual (including physiological decline, chronic disease, lifestyle, and physical activity) and occupational (including shift work, sleep deprivation, and cold/heat exposure) factors on the physical decline of older workers, and therefore the risk of work-related injuries or illness. [ABSTRACT FROM AUTHOR]

Bituminous material is a limited natural resource mainly used in hot mix asphalt production. The high costs coupled with the large amounts required have been forcing pavement engineers to find cost effective alternative materials that can be used as extenders or partial substitutes. This prohibitive cost factor led this paper to focus on the utilization of abundant granular sulphur as an extender for the more expensive bituminous material. In this study, sulphur-extended binders were prepared by using a 50/70 grade bitumen and by increasing the amounts of granular sulphur as an extension up to a maximum 50% by weight. The samples were then exposed to short and long-term aging by performing the rolling thin film oven and pressure aging vessel tests. Aged and virgin samples were then further tested using analytical, rheological, and morphological testing methods. The promising results demonstrate that the sulphur-extended binder not only increases the performance of the neat bitumen, but can also lower overall costs. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Animal Science is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The anabolic effects of nutrition on skeletal muscle may depend on adequate skeletal muscle perfusion, which is impaired in older people. Cocoa flavanols have been shown to improve flow-mediated dilation, an established measure of endothelial function. However, their effect on muscle microvascular blood flow is currently unknown. Therefore, the objective of this study was to explore links between the consumption of cocoa flavanols, muscle microvascular blood flow, and muscle protein synthesis (MPS) in response to nutrition in older men. To achieve this objective, leg blood flow (LBF), muscle microvascular blood volume (MBV), and MPS were measured under postabsorptive and postprandial (intravenous Glamin (Fresenius Kabi, Germany), dextrose to sustain glucose ~7.5 mmol·L-1) conditions in 20 older men. Ten of these men were studied with no cocoa flavanol intervention and a further 10 were studied with the addition of 350mgof cocoa flavanols at the same time that nutrition began. Leg (femoral artery) blood flow was measured by Doppler ultrasound, muscle MBV by contrast-enhanced ultrasound using Definity (Lantheus Medical Imaging, Mass., USA) perflutren contrast agent and MPS using [1, 2-13C2]leucine tracer techniques. Our results show that although older individuals do not show an increase in LBF or MBV in response to feeding, these absent responses are apparent when cocoa flavanols are given acutely with nutrition. However, this restoration in vascular responsiveness is not associated with improved MPS responses to nutrition. We conclude that acute cocoa flavanol supplementation improves muscle macro- and microvascular responses to nutrition, independently of modifying muscle protein anabolism. [ABSTRACT FROM AUTHOR]

This study examined the effects and feasibility of a twice-weekly combined therapy of branched-chain amino acids (BCAAs) and exercise on physical function improvement in frail and pre-frail elderly people requiring long-term care. We used a crossover design in which the combination of exercise and nutritional interventions was carried out twice a week during cycles A (3 months) and B (3 months) and the exercise intervention alone was performed during the washout period. The exercise intervention entailed the following 5 training sets: 3 sets of muscle training at 30% of maximum voluntary contraction, 1 set of aerobic exercise, and 1 set of balance training. For the nutritional intervention, 6 g of BCAAs or 6 g of maltodextrin was consumed 10 min before starting the exercise. We determined upper and lower limb isometric strength, performance on the Functional Reach Test (FRT) and the Timed Up and Go test, and activity level. In the comparison between the BCAA group and the control group after crossover, the improvement rates in gross lower limb muscle strength (leg press, knee extension) and FRT performance were significantly greater (by approximately 10%) in the BCAA group. In the comparison between different orders of BCAA administration, significant effects were shown for the leg press in both groups only when BCAAs were given. The combination of BCAA intake and exercise therapy yielded significant improvements in gross lower limb muscle strength and dynamic balance ability. [ABSTRACT FROM AUTHOR]

Resistance exercise is an efficacious stimulus for improving cognitive function in older adults, which may be mediated by the upregulation of blood-borne neurotrophic growth factors (NTFs) like brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1). However, the NTF response to resistance exercise and training in older adults is poorly understood. Therefore, the purpose of this study was to characterize the timing and magnitude of the NTF response following an acute bout of resistance exercise before and after 8 weeks of resistance training. Ten cognitively normal, older adults (ages 60-77 years, five men) were examined. The acute NTF response to resistance exercise was assessed via serum samples drawn at designated time points following exercise. This procedure was then repeated following 8 weeks of resistance training. BDNF increased immediately post-exercise (Δ9% pre-training, Δ11% post-training) then returned to resting levels while IGF-1 remained stable following resistance exercise before and after 8 weeks of resistance training. Basal levels of both NTFs were unaffected by the 8 week training period. We report a transient increase in serum BDNF following a bout of resistance exercise in older adults, which could have implications for the design of interventions seeking to maximize cognitive function in older adults. [ABSTRACT FROM AUTHOR]

Fast skeletal muscle troponin T ( TNNT3) is an important component of the skeletal muscle contractile machinery. The precursor mRNA (pre-mRNA) encoding TNNT3 is alternatively spliced, and changes in the pattern of TNNT3 splice form expression are associated with alterations in thin-filament calcium sensitivity and force production during muscle contraction and thereby regulate muscle function. Interestingly, during aging, the muscle force/cross-sectional area is reduced, suggesting that loss of mass does not completely account for the impaired muscle function that develops during the aging process. Therefore, in this study, we tested the hypothesis that age and changes in muscle loading are associated with alterations in Tnnt3 alternative splicing in the rat gastrocnemius muscle. We found that the relative abundance of several Tnnt3 splice forms varied significantly with age among 2-, 9-, and 18-month-old rats and that the pattern correlated with changes in body mass rather than muscle mass. Hindlimb immobilization for 7 days resulted in dramatic alterations in splice form relative abundance such that the pattern was similar to that observed in lighter animals. Remobilization for 7 days restored the splicing pattern toward that observed in the nonimmobilized limb, even though muscle mass had not yet begun to recover. In conclusion, the results suggest that Tnnt3 pre-mRNA alternative splicing is modulated rapidly (i.e., within days) in response to changes in the load placed on the muscle. Moreover, the results show that restoration of Tnnt3 alternative splicing to control patterns is initiated prior to an increase in muscle mass. [ABSTRACT FROM AUTHOR]

Aging leads to sarcopenia and loss of physical function. We examined whether voluntary wheel running, when combined with dietary supplementation with (−)-epigallocatechin-3-gallate (EGCG) and β-alanine (β-ALA), could improve muscle function and alter gene expression in the gastrocnemius of aged mice. Seventeen-month-old BALB/cByJ mice were given access to a running wheel or remained sedentary for 41 days while receiving either AIN-93M (standard feed) or AIN-93M containing 1.5 mg·kg−1 EGCG and 3.43 mg·kg−1 β-ALA. Mice underwent tests over 11 days from day 29 to day 39 of the study period, including muscle function testing (grip strength, treadmill exhaustive fatigue, rotarod). Following a rest day, mice were euthanized and gastrocnemii were collected for analysis of gene expression by quantitative PCR. Voluntary wheel running (VWR) improved rotarod and treadmill exhaustive fatigue performance and maintained grip strength in aged mice, while dietary intervention had no effect. VWR increased gastrocnemius expression of several genes, including those encoding interleukin-6 ( Il6, p = 0.001), superoxide dismutase 1 ( Sod1, p = 0.046), peroxisome proliferator-activated receptor gamma coactivator 1-α ( Ppargc1a, p = 0.013), forkhead box protein O3 ( Foxo3, p = 0.005), and brain-derived neurotrophic factor ( Bdnf, p = 0.008), while reducing gastrocnemius levels of the lipid peroxidation marker 4-hydroxynonenal ( p = 0.019). Dietary intervention alone increased gastrocnemius expression of Ppargc1a ( p = 0.033) and genes encoding NAD-dependent protein deacetylase sirtuin-1 ( Sirt1, p = 0.039), insulin-like growth factor I ( Igf1, p = 0.003), and macrophage marker CD11b ( Itgam, p = 0.016). Exercise and a diet containing β-ALA and EGCG differentially regulated gene expression in the gastrocnemius of aged mice, while VWR but not dietary intervention improved muscle function. We found no synergistic effects between dietary intervention and VWR. [ABSTRACT FROM AUTHOR]

Most research on sedentary behaviour has focused on cardiometabolic outcomes and markers of metabolic dysfunction, while neuromuscular outcomes have received less attention. The objective of the present study was to determine whether sedentary time is negatively associated with laboratory-based measures of lower body muscular strength and postural stability in middle-aged women. Forty-nine women (56.6 ± 4.1 years) participated in the study. Participants wore an ActiGraph GT3X accelerometer for 7 days to quantify sedentary time and physical activity. Following a familiarization session, assessments of lower body muscular strength and postural stability were performed. Peak torque of knee extensors and flexors was assessed using an isokinetic dynamometer. Postural stability was assessed using computerized dynamic posturography and a composite equilibrium score (CES) was calculated. Participants spent 9.4 ± 1.3 h per day (65% of wear time) sedentary and 28.2 ± 17.3 min per day (3.3% of wear time) in moderate to vigorous physical activity (MVPA). Postural stability and relative peak torque of the knee flexors were significantly associated with time spent sedentary ( r = -0.35, p = 0.01 and r = -0.31, p = 0.03, respectively). Multiple linear regression analyses showed that after adjusting for MVPA, sedentary time was not significantly related to either CES or peak torque of the knee extensors or flexors. In contrast to our hypothesis, postural stability and leg strength were not independently related to sedentary time. While sedentary behaviour may be an important risk factor for cardiometabolic disease, the present results suggest MVPA may be more important to neuromuscular outcomes. [ABSTRACT FROM AUTHOR]

β cell dysfunction is central to the development and progression of type 2 diabetes (T2D). T2D develops when β cells are not able to compensate for the increasing demand for insulin caused by insulin resistance. Epigenetic modifications play an important role in establishing and maintaining β cell identity and function in physiological conditions. On the other hand, epigenetic dysregulation can cause a loss of β cell identity, which is characterized by reduced expression of genes that are important for β cell function, ectopic expression of genes that are not supposed to be expressed in β cells, and loss of genetic imprinting. Consequently, this may lead to β cell dysfunction and impaired insulin secretion. Risk factors that can cause epigenetic dysregulation include parental obesity, an adverse intrauterine environment, hyperglycemia, lipotoxicity, aging, physical inactivity, and mitochondrial dysfunction. These risk factors can affect the epigenome at different time points throughout the lifetime of an individual and even before an individual is conceived. The plasticity of the epigenome enables it to change in response to environmental factors such as diet and exercise, and also makes the epigenome a good target for epigenetic drugs that may be used to enhance insulin secretion and potentially treat diabetes. [ABSTRACT FROM AUTHOR]

Protein is an essential component of a healthy diet and is a focus of research programs seeking to optimize health at all stages of life. The focus on protein as a nutrient often centers on its thermogenic and satiating effect, and when included as part of a healthy diet, its potential to preserve lean body mass. A growing body of literature, including stable isotope based studies and longer term dietary interventions, suggests that current dietary protein recommendations may not be sufficient to promote optimal muscle health in all populations. A protein intake moderately higher than current recommendations has been widely endorsed by many experts and working groups and may provide health benefits for aging populations. Further, consuming moderate amounts of high-quality protein at each meal may optimally stimulate 24-h muscle protein synthesis and may provide a dietary platform that favors the maintenance of muscle mass and function while promoting successful weight management in overweight and obese individuals. Dietary protein has the potential to serve as a key nutrient for many health outcomes and benefits might be increased when combined with adequate physical activity. Future studies should focus on confirming these health benefits from dietary protein with long-term randomized controlled studies. [ABSTRACT FROM AUTHOR]

Older adults better maintain eccentric strength relative to isometric strength, as indicated by a higher ratio of eccentric:isometric torque as compared with younger adults. The effect of increasing angular velocities (>200°/s) on the age-related maintenance of eccentric strength has not been tested and thus it is unknown whether the eccentric:isometric ratio is velocity dependent in old age. The purpose of this study was to investigate eccentric strength of the ankle dorsiflexors over a large range of lengthening angular velocities in young and older men. Isometric neuromuscular properties were assessed on a HUMAC NORM dynamometer. Nine young (∼24 years) and 9 older (∼76 years) healthy men performed maximal voluntary eccentric contractions at angular velocities of 15-360°/s. Despite near full voluntary activation (>95%), the older men were ∼30% weaker than the young men for isometric strength ( P < 0.05). Across all lengthening velocities, older men had a greater eccentric:isometric ratio than young men ( P < 0.05). Additionally, there was a velocity dependence of strength in both young and older men: eccentric strength increased as velocity increased up to 120°/s ( P < 0.05) and plateaued thereafter. In young and older men, eccentric strength at 15°/s was ∼20% and ∼40% greater than isometric strength ( P < 0.05), while at 360°/s eccentric strength was ∼50% and ∼90% greater, respectively ( P < 0.05). These findings indicate that with increasing angular velocity, both young and older men have considerable increases in the eccentric:isometric ratio of torque production. [ABSTRACT FROM AUTHOR]

Creatine supplementation in close proximity to resistance training may be an important strategy for increasing muscle mass and strength; however, it is unknown whether creatine supplementation before or after resistance training is more effective for aging adults. Using a double-blind, repeated measures design, older adults (50-71 years) were randomized to 1 of 3 groups: creatine before (CR-B: n = 15; creatine (0.1 g/kg) immediately before resistance training and placebo (0.1 g/kg cornstarch maltodextrin) immediately after resistance training), creatine after (CR-A: n = 12; placebo immediately before resistance training and creatine immediately after resistance training), or placebo (PLA: n = 12; placebo immediately before and immediately after resistance training) for 32 weeks. Prior to and following the study, body composition (lean tissue, fat mass; dual-energy X-ray absorptiometry) and muscle strength (1-repetition maximum leg press and chest press) were assessed. There was an increase over time for lean tissue mass and muscle strength and a decrease in fat mass ( p < 0.05). CR-A resulted in greater improvements in lean tissue mass (Δ 3.0 ± 1.9 kg) compared with PLA (Δ 0.5 ± 2.1 kg; p < 0.025). Creatine supplementation, independent of the timing of ingestion, increased muscle strength more than placebo (leg press: CR-B, Δ 36.6 ± 26.6 kg; CR-A, Δ 40.8 ± 38.4 kg; PLA, Δ 5.6 ± 35.1 kg; chest press: CR-B, Δ 15.2 ± 13.0 kg; CR-A, Δ 15.7 ± 12.5 kg; PLA, Δ 1.9 ± 14.7 kg; p < 0.025). Compared with resistance training alone, creatine supplementation improves muscle strength, with greater gains in lean tissue mass resulting from post-exercise creatine supplementation. [ABSTRACT FROM AUTHOR]

Limited functional mobility in older adults has been associated with declines in tests of motor, psychomotor, and executive function. Animal studies have demonstrated reversals in indices of motor and psychomotor function via supplementation with polyphenolic-rich foods such as blueberries. The purpose of this study was to examine whether 6 weeks of daily consumption of 2 cups of frozen blueberries affects functional mobility in older adults. Pre- and post-intervention assessments of grip strength, simple reaction time, adaptive gait, and executive function were completed for older adults (age >60 years) partially randomly assigned to a blueberry (BB) supplementation or a carrot juice drink control (CAR) group. Paired t tests were used to assess within-group effects for outcome variables in each supplementation group, and a mixed-model analysis of covariance (ANCOVA) was used to determine group (CAR vs. BB) differences. Mixed-model analysis indicated that the BB group demonstrated significant improvements relative to the CAR group in performance (i.e., number of step errors) of a challenging dual-task adaptive gait test that were independent of differences in gait speed. Within only the BB group, significant improvements were also seen in 3 other measures (i.e., usual gait speed; number of step errors during single-task adaptive gait; and gait speed during dual-task adaptive gait). These preliminary findings support the hypothesis that blueberry supplementation may provide an effective countermeasure to age-related declines in functional mobility and serve as justification for an expansion to larger trials to more fully assess this nonpharmacologic approach to maintaining optimal mobility and independence. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate how physical fitness level could affect antioxidant activity and malondialdehyde (MDA) level at rest and in response to exhaustive exercise in healthy older adults. Fifty older adults (average age: 66.1 ± 3.8 years) were divided according to their physical fitness level into an unfit group (UG) ( n = 15), a low fitness level group (LFG) ( n = 18), and a high fitness level group (HFG) ( n = 17). Fitness status was classified based on answers to a questionnaire about physical activity in the previous 12 months. Before and after an incremental cycle ergometer test to exhaustion, the following markers were assessed: superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase, ascorbic acid, α-tocopherol, and MDA. At rest, SOD, GPX, and α-tocopherol activities were higher in the HFG ( p < 0.05), whereas MDA level was lower in the LFG in comparison with the 2 other groups ( p < 0.05). During the postexercise period, antioxidant activity increased only in the LFG and the HFG (GPX, SOD, and α-tocopherol). MDA level increased in all groups after the exercise ( p < 0.05). In addition, MDA level was higher during the recovery period in the HFG as compared with the others groups. This study concluded that both low and high physical fitness levels help maintain better antioxidant defenses in older adults. However, a higher physical fitness level, rather than a lower physical fitness level, could increase lipid peroxidation. [ABSTRACT FROM AUTHOR]

Glycine has been used to reduce oxidative stress and proinflammatory mediators in some metabolic disorders; however, its effect on the vasculature has been poorly studied. The aim of this work was to explore the effect of glycine on endothelial dysfunction in aged rats. Aortic rings with intact or denuded endothelium were obtained from untreated or glycine-treated male Sprague-Dawley rats at 5 and 15 months of age. Concentration-response curves to phenylephrine (PHE) were obtained from aortic rings incubated with NG-nitro- l-arginine methyl ester ( l-NAME), superoxide dismutase (SOD), indomethacin, SC-560, and NS-398. Aortic mRNA expression of endothelial nitric oxide synthase (eNOS), NADPH oxidase 4 (NOX-4), cyclooxygenase 1 (COX-1), cyclooxygenase 2 (COX-2), tumour necrosis factor (TNF)-α, and interleukin-1 β was measured by real time RT-PCR. The endothelial modulation of the contraction by PHE was decreased in aortic rings from aged rats. Glycine treatment improved this modulator effect and increased relaxation to acetylcholine. Glycine augmented the sensitivity for PHE in the presence of l-NAME and SOD. It also reduced the contraction by incubation with indomethacin, SC-560, and NS-398. Glycine increased the mRNA expression of eNOS and decreased the expression of COX-2 and TNF-α. Glycine improved the endothelium function in aged rats possibly by enhancing eNOS expression and reducing the role of superoxide anion and contractile prostanoids that increase the nitric oxide bioavailability. [ABSTRACT FROM AUTHOR]

Homozygosity for the common nonsense polymorphism R577X in the α-actinin-3 gene ( ACTN3) causes complete α-actinin-3 deficiency in fast-twitch skeletal muscle fibers. This study investigated whether the ACTN3 R577X polymorphism affects fitness status using a battery of tests in a large Japanese cohort. In the present study, 1227 subjects (age: 25-85 years) were genotyped for the ACTN3 R577X polymorphism (rs1815739) using a TaqMan SNP genotyping assay (Applied Biosystems). All subjects were divided into 2 groups based on their age (<55 years and ≥55 years). All subjects completed a questionnaire about exercise habits and were subjected to a battery of tests to assess their fitness status (including grip strength test, chair stand test, and 8-foot walking test). A significant association between the ACTN3 R577X genotype and chair stand test performance was observed in the group of men ≥55 using ANCOVA adjusted for age and exercise habits ( p = 0.036). The ACTN3 R577X genotype accounted for 2.5% of the variability in the results of the chair stand test among men in the ≥55 age group. Moreover, for the ≥55 age group, performance in the chair stand test was lower among those with the XX genotype than among those with the RR genotype ( p = 0.024) or RX genotype ( p = 0.005), unlike results for the <55 age group. No significant difference was noted for hand grip strength or 8-foot walking time. Thus, our results suggest that the ACTN3 R577X genotype is associated with lower-extremity muscle function in the Japanese population. [ABSTRACT FROM AUTHOR]

This study examined the age-related decline in endurance running performance of one of the greatest master runners ever, Ed Whitlock, who died recently. His running performances from 1500 m to marathon were analyzed for 5 periods of 5 years from 65-69 years to 85-89 years. Despite exceptional running performances for his advanced age, the rate of decline in his performances increased after 80 years and was drastically amplified after 85 years. [ABSTRACT FROM AUTHOR]

Implication of reactive oxygen species/oxidative stress has been readily reported in etiology of aging and related manifestations. Plasma membrane as a regulator of numerous aspects of cell physiology including cell-cell interaction, solute transport, and signal transduction, provides structural integrity to the cells. The aim of the present study was to determine the effect of resveratrol administration in vitro, to evaluate the biological effect of this phytoalexin in oxidatively injured erythrocytes during aging. This study, carried out on 91 normal healthy subjects, provides experimental evidence that erythrocytes have increased oxidative damage with age. In vitro administration of resveratrol significantly attenuated deleterious effects of oxidative injury in erythrocytes from humans of all ages. [ABSTRACT FROM AUTHOR]

In animal mitochondria, the four electron reduction of molecular oxygen to produce water at respiratory complex IV is the terminal step in substrate oxidation. However, respiratory complexes I, II, and III can participate in the single electron reduction of oxygen to produce the radical species superoxide. This progenitor reactive oxygen species (ROS) participates in a number of reactions that generate other ROS. These molecules may react with, and damage, intracellular macromolecules, leading to cellular dysfunction. Mitochondrial ROS production is often considered from this perspective of macromolecular damage and is central to the 'oxidative damage theory of aging', which suggests the accumulation of oxidative damage in animal cells underlies the aging phenotype and limits lifespan. In this review, we discuss some experimental results accumulated over the past decade that are inconsistent with this theory. A limitation of the theory is that it presupposes mitochondrial ROS are inherently harmful. However, it is increasingly apparent that some basic cellular functions are physiologically regulated by normal levels of mitochondrial ROS. For example, cell growth and division, the apoptotic pathway, and mitochondrial fusion-fission dynamics all appear to be redox-regulated by mitochondrial ROS and perhaps the matrix manganese superoxide dismutase (MnSOD). Therefore, it is less clear how the balance between ROS regulation of normal cellular activities and ROS-mediated macromolecular damage is maintained and how this relates to aging and longevity in animals. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Zoology is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Obesity is associated with increased risk of many types of cancer. Less is known regarding associations between adipose depots and cancer risk. We aimed to explore relationships between adipose depots, risk of cancer, and obesity-related cancer (per NCI definition) in participants initially aged 70-79 years without prevalent cancer (1179 men, 1340 women), and followed for incident cancer for 13 years. Measures included body mass index (BMI), total adipose tissue from dual-energy X-ray absorptiometry, and computed tomography measures of visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue, thigh intermuscular adipose tissue, and thigh muscle attenuation (Hounsfield unit, HU), where low HU indicates fatty infiltration. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards models adjusted for demographics, lifestyle variables, and medical conditions. During follow-up, 617 participants developed cancer of which 224 were obesity-related cancers. Total adipose tissue and VAT were positively associated with cancer risk among women (HR 1.14, 95% CI 1.01-1.30 per SD increase; HR 1.15, 95% CI 1.02-1.30 per SD increase). There were no associations with cancer risk among men. Total adipose tissue was positively associated with obesity-related cancer risk among women (HR 1.23, 95% CI 1.03-1.46 per SD increase). VAT was positively associated with obesity-related cancer risk among men (HR 1.30, 95% CI 1.06-1.60 per SD increase) and remained associated even with adjustment for BMI (HR 1.40, 95% CI 1.08-1.82 per SD increase). These findings provide insight into relationships between specific adipose depots and cancer risk and suggest differential relationships among men and women. [ABSTRACT FROM AUTHOR]

Copyright of Applied Physiology, Nutrition & Metabolism is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Heat waves are the cause of many preventable deaths around the world, especially among older adults and in countries with more temperate climates. In the present study, we examined the effects of age on whole-body heat loss and heat storage during passive exposure to environmental conditions representative of the upper temperature extremes experienced in Canada. Direct and indirect calorimetry measured whole-body evaporative heat loss and dry heat exchange, as well as the change in body heat content. Twelve younger (21 ± 3 years) and 12 older (65 ± 5 years) adults with similar body weight (younger: 72.0 ± 4.4 kg; older: 80.1 ± 4.2 kg) and body surface area (younger: 1.8 ± 0.1 m2; older: 2.0 ± 0.1 m2) rested for 2 h in a hot-dry [36.5 °C, 20% relative humidity (RH)] or hot-humid (36.5 °C, 60% RH) environment. In both conditions, evaporative heat loss was not significantly different between groups (dry: p = 0.758; humid: p = 0.814). However, the rate of dry heat gain was significantly greater (by approx. 10 W) for older adults relative to younger adults during the hot-dry ( p = 0.032) and hot-humid exposure ( p = 0.019). Consequently, the cumulative change in body heat content after 2 h of rest was significantly greater in older adults in the hot-dry (older: 212 ± 25 kJ; younger: 131 ± 27 kJ, p = 0.018) as well as the hot-humid condition (older: 426 ± 37 kJ; younger: 317 ± 45 kJ, p = 0.037). These findings demonstrate that older individuals store more heat during short exposures to dry and humid heat, suggesting that they may experience increased levels of thermal strain in such conditions than people of younger age. [ABSTRACT FROM AUTHOR]

Age-related chronic low-grade inflammation may render older individuals more susceptible to heat illnesses. The purpose of this study was to examine the influence of intermittent work in the heat on the circulating cytokine responses of older workers. Fourteen young (aged 25.6 ± 0.7 years) and older (aged 57.7 ± 1.5 years) males, matched for body surface area, cycled for 4 × 15 min (separated by 15-min rest) at moderate to heavy intensity (400 W heat production) in warm/dry (35 °C, 20% relative humidity (RH)) and warm/humid (35 °C, 60% RH) conditions. Rectal (Tre) and mean skin (MTsk) temperatures and heart rate were measured continuously, ratings of perceived exertion and thermal sensation recorded at the end of each exercise bout, and blood samples at baseline (PRE) and following the final 60-min recovery (POST) were analyzed for interleukin (IL)-6, tumor necrosis factor (TNF)-α, and percent changes in blood (BV) and plasma (PV) volumes. No differences were observed between the age groups for Tre, MTsk, heart rate, perceptual strain, or percentage of changes in BV, PV, or ΔTNF-α. Under both conditions, the older males had elevated IL-6 and TNF-α (PRE, POST) compared with the young males. ΔIL-6 tended to be greater in the warm/humid condition (+2.53 ± 0.49 and +1.52 ± 0.41 pg·mL−1) compared with the warm/dry condition (+1.02 ± 0.13 and +0.68 ± 0.18 pg·mL−1) for older but not young males, respectively. Young and older males experienced similar thermal, cardiovascular, and perceptual strain within the warm/dry and warm/humid conditions. [ABSTRACT FROM AUTHOR]

Postmenopausal women experience an age-related decline in resting energy expenditure (REE), which is a risk factor for energy imbalance and metabolic disease. Exercise, because of its association with greater lean tissue mass and other factors, has the potential to mediate REE decline, but the relation between exercise and REE in postmenopausal women is not well characterized. This study tests the hypothesis that exercise energy expenditure (EEE) is positively associated with REE and can counter the effects of age and menopause. It involves a cross-sectional sample of 31 healthy postmenopausal women (aged 49-72 years) with habitual exercise volumes at or above levels consistent with current clinical recommendations. Subjects kept exercise diaries for 4 weeks that quantified exercise activity and were measured for body composition, maximal oxygen uptake, and REE. Multiple regression analysis was used to test for associations between EEE, age, body composition, and REE. There was a significant positive relation between EEE and lean tissue mass (fat-free mass and fat-free mass index). The relation between REE and EEE remained significant even after controlling for lean tissue mass. These results support the hypothesis that exercise is positively associated with REE and can counter the negative effects of age and menopause. They also indicate a continuous relation between exercise and REE across ranges of exercise, from moderate to high. Exercise at levels that are at or above current clinical guidelines might, in part, ameliorate the risk for energy imbalance and metabolic disease because of its positive relation with REE. [ABSTRACT FROM AUTHOR]