Lung function predicts mortality; whether it is associated with functional status in the general population remains unclear. This study examined the association of lung function with multiple measures of functioning in early old age. Data are drawn from the Whitehall II study; data on lung function (forced expiratory volume in 1 s, height FEV1), walking speed (2.44 m), cognitive function (memory and reasoning) and self-reported physical and mental functioning (SF-36) were available on 4,443 individuals, aged 50–74 years. In models adjusted for age, 1 standard deviation (SD) higher height-adjusted FEV1 was associated with greater walking speed (beta = 0.16, 95% CI: 0.13, 0.19), memory (beta = 0.09, 95% CI: 0.06, 0.12), reasoning (beta = 0.16, 95% CI: 0.13, 0.19) and self-reported physical functioning (beta = 0.13, 95% CI: 0.10, 0.16). Socio-demographic measures, health behaviours (smoking, alcohol, physical activity, fruit/vegetable consumption), body mass index (BMI) and chronic conditions explained two-thirds of the association with walking speed and self-assessed physical functioning and over 80% of the association with cognitive function. Our results suggest that lung function is a good ‘summary’ measure of overall functioning in early old age.

Lung function predicts mortality, whether it is associated with functional status in the general population remains unclear. This study examined the association of lung function with multiple measures of functioning in early old age. Data are drawn from the Whitehall II study; data on lung function (forced expiratory volume in one second, height FEV1), walking speed (over 2.44 m), cognitive function (memory and reasoning), and self-reported physical and mental functioning (SF-36) were available on 4443 individuals, aged 50–74 years. In models adjusted for age, one standard deviation (SD) higher height-adjusted FEV1 was associated with greater walking speed (beta=0.16, 95% CI: 0.13, 0.19), memory (beta=0.09, 95% CI: 0.06, 0.12), reasoning (beta=0.16, 95% CI: 0.13, 0.19), and self-reported physical functioning (beta=0.13, 95% CI: 0.10, 0.16). Socio-demographic measures, health behaviours (smoking, alcohol, physical activity, fruit/vegetable consumption), BMI and chronic conditions explained two-thirds of the association with walking speed and self-assessed physical functioning and over 80% of the association with cognitive function. Our results suggest that lung function is a good “summary” measure of overall functioning in early old age.

A third of those over 80 years of age are likely to have dementia, the lack of a cure requires efforts directed at prevention and delaying the age of onset. We argue here for the importance of understanding the cognitive ageing process, seen as the decline in various cognitive functions from adulthood to old age. The impact of age on cognitive function is heterogeneous and the identification of risk factors associated with adverse cognitive ageing profiles would allow well-targeted interventions, behavioural or pharmacological, to delay and reduce the population burden of dementia. A shift away from binary outcomes such as dementia assessed at one point in time in elderly populations to research on cognitive ageing using repeated measures of cognitive function and starting earlier in the life course would allow the sources of variability in ageing to be better understood.

A third of those over 80 years of age are likely to have dementia, the lack of a cure requires efforts directed at prevention and delaying the age of onset. We argue here for the importance of understanding the cognitive ageing process, seen as the decline in various cognitive functions from adulthood to old age. The impact of age on cognitive function is heterogeneous and the identification of risk factors associated with adverse cognitive ageing profiles would allow well targeted interventions, behavioural or pharmacological, to delay and reduce the population burden of dementia. A shift away from binary outcomes such as dementia assessed at one point in time in elderly populations to research on cognitive ageing using repeated measures of cognitive function and staring earlier in the lifecourse would allow the sources of variability in ageing to be better understood.

In humans the circulating concentrations of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) decrease markedly during aging, and have been implicated in age-associated cognitive decline. This has led to the hypothesis that DHEA supplementation during aging may improve memory. In rodents, a cognitive anti-aging effect of DHEA and DHEAS has been observed but it is unclear whether this effect is mediated indirectly through conversion of these steroids to estradiol. Moreover, despite the demonstration of correlations between endogenous DHEA concentrations and cognitive ability in certain human patient populations, such correlations have yet to be convincingly demonstrated during normal human aging. This review highlights important differences between rodents and primates in terms of their circulating DHEA and DHEAS concentrations, and suggests that age-related changes within the human DHEA metabolic pathway may contribute to the relative inefficacy of DHEA replacement therapies in humans. The review also highlights the value of using nonhuman primates as a pragmatic animal model for testing the therapeutic potential of DHEA for age-associate cognitive decline in humans.

In humans the circulating concentrations of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) decrease markedly during aging, and have been implicated in age-associated cognitive decline. This has led to the hypothesis that DHEA supplementation during aging may improve memory. In rodents, a cognitive anti-aging effect of DHEA and DHEAS has been observed but it is unclear whether this effect is mediated indirectly through conversion of these steroids to estradiol. Moreover, despite the demonstration of correlations between endogenous DHEA concentrations and cognitive ability in certain human patient populations, such correlations have yet to be convincingly demonstrated during normal human aging. This review highlights important differences between rodents and primates in terms of their circulating DHEA and DHEAS concentrations, and suggests that age-related changes within the human DHEA metabolic pathway may contribute to the relative inefficacy of DHEA replacement therapies in humans. The review also highlights the value of using nonhuman primates as a pragmatic animal model for testing the therapeutic potential of DHEA for age-associate cognitive decline in humans.

Sulfur amino acids are determinant for the detoxification of paracetamol (N-acetyl-p-aminophenol) through sulfate and glutathione conjugations. Long-term paracetamol treatment is common in the elderly, despite a potential cysteine/glutathione deficiency. Detoxification could occur at the expense of anti-oxidative defenses and whole body protein stores in elderly. We tested how older persons satisfy the extra demand in sulfur amino acids induced by long-term paracetamol treatment, focusing on metabolic and nutritional aspects. Effects of 3 g/day paracetamol for 14 days on fasting blood glutathione, plasma amino acids and sulfate, urinary paracetamol metabolites, and urinary metabolomic were studied in independently living older persons (five women, five men, mean (±SEM) age 74 ± 1 years). Dietary intakes were recorded before and at the end of the treatment and ingested sulfur amino acids were evaluated. Fasting blood glutathione, plasma amino acids, and sulfate were unchanged. Urinary nitrogen excretion supported a preservation of whole body proteins, but large-scale urinary metabolomic analysis revealed an oxidation of some sulfur-containing compounds. Dietary protein intake was 13% higher at the end than before paracetamol treatment. Final sulfur amino acid intake reached 37 mg/kg/day. The increase in sulfur amino acid intake corresponded to half of the sulfur excreted in urinary paracetamol conjugates. In conclusion, older persons accommodated to long-term paracetamol treatment by increasing dietary protein intake without any mobilization of body proteins, but with decreased anti-oxidative defenses. The extra demand in sulfur amino acids led to a consumption far above the corresponding population-safe recommendation.

Reduced signaling of the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) pathway is associated with extended life span in several species. Ames dwarf mice are GH-deficient and live >50% longer than wild-type littermates. Previously, we have shown that tissues from Ames mice exhibit elevated levels of antioxidative enzymes, less H2O2 production, and lower oxidative damage suggesting that mitochondrial function may differ between genotypes. To explore the relationship between hormone deficiency and mitochondria in mice with extended longevity, we evaluated activity, protein, and gene expression of oxidative phosphorylation components in dwarf and wild-type mice at varying ages. Liver complex I + III activity was higher in dwarf mice compared to wild-type mice. The activity of I + III decreased between 3 and 20 months of age in both genotypes with greater declines in wild-type mice in liver and skeletal muscle. Complex IV activities in the kidney were elevated in 3- and 20-month-old dwarf mice relative to wild-type mice. In Ames mice, protein levels of the 39 kDa complex I subunit were elevated at 20 months of age when compared to wild-type mouse mitochondria for every tissue examined. Kidney and liver mitochondria from 20-month-old dwarf mice had elevated levels of both mitochondrially-encoded and nuclear-encoded complex IV proteins compared to wild-type mice (p < 0.05). Higher liver ANT1 and PGC-1α mRNA levels were also observed in dwarf mice. Overall, we found that several components of the oxidative phosphorylation (OXPHOS) system were elevated in Ames mice. Mitochondrial to nuclear DNA ratios were not different between genotypes despite the marked increase in PGC-1α levels in dwarf mice. The increased OXPHOS activities, along with lower ROS production in dwarf mice, predict enhanced mitochondrial function and efficiency, two factors likely contributing to long-life in Ames mice.

Tubular aggregates (TAs), ordered arrays of elongated sarcoplasmic reticulum (SR) tubules, are present in skeletal muscle from patients with myopathies and are also experimentally induced by extreme anoxia. In wild-type mice TAs develop in a clear age-, sex- (male), and fiber type- (fast twitch) dependence. However, the events preceding the appearance of TAs have not been explored. We investigated the sequential stages leading to the initial appearance and maturation of TAs in EDL from male mice. TAs’ formation requires two temporally distinct steps that operate via different mechanisms. Initially (before 1 year of age), the SR Ca2+ binding protein calsequestrin (CASQ) accumulates specifically at the I band level causing swelling of free SR cisternae. In the second stage, the enlarged SR sacs at the I band level extend into multiple, longitudinally oriented tubules with a full complement of sarco(endo)plasmic reticulum Ca2+ ATPases (SERCA) in the membrane and CASQ in the lumen. Tubules gradually acquire a regular cylindrical shape and uniform size apparently in concert with partial crystallization of SERCA. Multiple, small TAs associate to form fewer mature TAs of very large size. Interestingly, in fibers from CASQ1-knockout mice abnormal aggregates of SR tubules have different conformation and never develop into ordered aggregates of straight cylinders, possibly due to lack of CASQ accumulation. We conclude that TAs do not arise abruptly but are the final result of a gradually changing SR architecture and we suggest that the crystalline ATPase within the aggregates may be inactive.

Mitochondrial haplogroups could influence individual susceptibility to mitochondrial DNA (mtDNA) damage, and human longevity, as indicated by previous studies with Caucasian (European) or Asian cohorts. Here, we compared the frequency of mtDNA haplogroups in a group of Spanish (Caucasian) centenarians (n = 65, aged 100–108 years, 58 women, most from the central part of Spain) and a group of healthy young adults (n = 138, 62 women, aged 20–40 years) of the same ethnic origin. We did not find significant differences between centenarians and the control group (P > 0.2). Only two centenarians (both women) had the haplogroup J, which hampered comparison with the control group (n = 15, five women). Our data confirm that the potential effects of mitochondrial haplogroups on human longevity might be population/geographic specific, with important differences between studies (notably, with regard to the previously reported potential benefit brought about by the haplogroup J) arising from the different living environment and ethnic background of the study cohorts.

Previous research has shown a progressive deterioration in cognitive performance in rats exposed to 56Fe particles as a function of age. The present experiment was designed to evaluate the effects of age of irradiation independently of the age of testing. Male Fischer-344 rats, 2, 7, 12, and 16 months of age, were exposed to 25–200 cGy of 56Fe particles (1,000 MeV/n). Following irradiation, the rats were trained to make an operant response on an ascending fixed-ratio reinforcement schedule. When performance was evaluated as a function of both age of irradiation and testing, the results showed a significant effect of age on the dose needed to produce a performance decrement, such that older rats exposed to lower doses of 56Fe particles showed a performance decrement compared to younger rats. When performance was evaluated as a function of age of irradiation with the age of testing held constant, the results indicated that age of irradiation was a significant factor influencing operant responding, such that older rats tested at similar ages and exposed to similar doses of 56Fe particles showed similar performance decrements. The results are interpreted as indicating that the performance decrement is not a function of age per se, but instead is dependent upon an interaction between the age of irradiation, the age of testing, and exposure to HZE particles. The nature of these effects and how age of irradiation affects cognitive performance after an interval of 15 to 16 months remains to be established.

Impaired or deficient autophagy is believed to cause or contribute to aging, as well as several age-related pathologies. Thymic epithelial cells had a high constitutive level of autophagy. The autophagic process may play a supporting role or even a crucial role in the presentation of self-Ags in the thymus to shape the T-cell repertoires. Autophagic activity in the liver is important for the balance of energy and nutrients for basic cell functions. The abundance of autophagic structure in both cortical and medullary thymic epithelial cells and liver with mouse age has not been examined in detail. Here, we demonstrated that the architecture of mouse thymus and liver markedly changed with age. We found that the expression of LC3 detected by immunofluorescence and Western blot analysis was greatly decreased in thymus and liver of 12-month-old mice. The same level of reduction was observed in thymus and liver of 24-month-old mice. Ultrastructure analysis by an electron microscope revealed that the number of autophagic structure/vacuole in total thymic epithelial cells and hepatocytes decrease with age. The age-related decrease of autophagic structure in thymic epithelial cells may cause the reduction of immunocompetent T-cell pool in aged mice. The age-related decrease of autophagy in liver may induce accumulation of cellular materials in liver of aged mice.

Epigenetic variations have been widely described to occur during the aging process. To verify if these modifications are correlated with the inter-individual phenotypic variability of elderly people, we searched for a correlation between global DNA methylation levels and frailty. We found that the global DNA methylation levels were correlated to the frailty status in middle/advanced-aged subjects but not with age. A 7-year follow-up study also revealed that a worsening in the frailty status was associated to a significant decrease in the global DNA methylation levels. These results suggest that the relaxation of the epigenetic control in aging is specifically associated with the functional decline rather than with the chronological age of individuals. Thus, the modifications of DNA methylation, representing a drawbridge between the genetic and the environmental factors affecting the age-related decay of the organism, may play an important role in determining physiological changes over old age.

The indication for testosterone therapy in aging hypogonadal men without hypothalamic, pituitary, or testicular disease remains to be elucidated. The aim of this study was to investigate the effect of testosterone therapy on insulin sensitivity, substrate metabolism, body composition, and lipids in aging men with low normal bioavailable testosterone levels using a predefined cutoff level for bioavailable testosterone. A randomized, double-blinded, placebo-controlled study of testosterone treatment (gel) was done on 38 men, aged 60–78 years, with bioavailable testosterone <7.3 nmol/l and a waist circumference >94 cm. Insulin-stimulated glucose disposal (Rd) and substrate oxidation were assessed by euglycemic hyperinsulinemic clamps combined with indirect calorimetry. Lean body mass (LBM) and total fat mass (TFM) were measured by dual x-ray absorptiometry, and serum total testosterone was measured by tandem mass spectrometry. Bioavailable testosterone was calculated. Coefficients (b) represent the placebo-controlled mean effect of intervention. LBM (b = 1.9 kg, p = 0.003) increased while HDL–cholesterol (b = −0.12 mmol/l, p = 0.043) and TFM decreased (b = −1.2 kg, p = 0.038) in the testosterone group compared to placebo. Basal lipid oxidation (b = 5.65 mg/min/m2, p = 0.045) increased and basal glucose oxidation (b = −9.71 mg/min/m2, p = 0.046) decreased in response to testosterone therapy even when corrected for changes in LBM. No significant changes in insulin-stimulated Rd was observed (b = −0.01mg/min/m2, p = 0.92). Testosterone therapy increased muscle mass and lipid oxidation in aging men with low normal bioavailable testosterone levels; however, our data did not support an effect of testosterone on whole-body insulin sensitivity using the euglycemic hyperinsulinemic clamp technique.

A large array of gene involved in human longevity seems to be in relationship with insulin/IGF1 pathway. However, if such genes interact each other, or with other genes, to reduce the age-related metabolic derangement and determine the long-lived phenotype has been poorly investigated. Thus, we tested the role of interchromosomal interactions among IGF1R, IRS2, and UCP2 genes on the probability to reach extreme old age in 722 unrelated Italian subjects (401 women and 321 men; mean age, 62.83 ± 25.30 years) enrolled between 1998 and 1999. In particular, the G/A-IGF1R, Gly/Asp-IRS2, and Ala/Val-UCP2 allele combination was tested for association with longevity, metabolic profile and energy expenditure parameters. The effect on all-cause and cause-specific mortality rate was also assessed after a mean follow-up of 6 years. The analysis revealed that AAV allele combination is associated with a decreased all-cause mortality risk (HR, 0.72; 95% CI, 0.63–0.91; p = 0.03) and with a higher probability to reach the extreme of old age (OR, 3.185; 95% CI, 1.63–6.19; p = 0.0006). The analysis also revealed lower HOMA-IR (Diff, −0.532, 95% CI, 0.886–0.17; p = 0.003), higher respiratory quotient (Diff, 0.0363, 95% CI, 0.014–0.05; p = 0.001), and resting metabolic rate (Diff, 101.80693, 95% CI, −5.26–204.278; p = 0.038) for AAV allele combination. In conclusion, A-IGF1R/Asp-IRS2/Val-UCP2 allele combination is associated with a decreased all-cause mortality risk and with an increased chance of longevity. Such an effect is probably due to the combined effect of IGF1R, IRS2, and UCP2 genes on energy metabolism and on the age-related metabolic remodeling capacity.

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Angiotensin II (Ang II), a major effector of the renin–angiotensin system, is now recognized as a pro-inflammatory mediator. This Ang II signaling, which causes transcription of pro-inflammatory genes, is regulated through nuclear factor-κB (NF-κB). At present, the molecular mechanisms underlying the effect of aging on Ang II signaling and NF-κB activation are not fully understood. The purpose of this study was to document altered molecular events involved in age-related changes in Ang II signaling and NF-κB activation. Experimentations were carried out using kidney tissues from Fischer 344 rats at 6, 12, 18, and 24 months of age, and the rat endothelial cell line, YPEN-1 for the detailed molecular work. Results show that increases in Ang II and Ang II type 1 receptor during aging were accompanied by the generation of reactive species. Increased Ang II activated NF-κB by phosphorylating IκBα and p65. Increased phosphorylation of p65 at Ser 536 was mediated by the enhanced phosphorylation of IκB kinase αβ, while phosphorylation site Ser 276 of p65 was mediated by upregulated mitogen-activated and stress-activated protein kinase-1. These altered molecular events in aged animals were partly verified by experiments using YPEN-1 cells. Collectively, our findings provide molecular insights into the pro-inflammatory actions of Ang II, actions that influence the phosphorylation of p65-mediated NF-κB activation during aging. Our study demonstrates the age-related pleiotropic nature of the physiologically important Ang II can change into a deleterious culprit that contributes to an increased incidence of many chronic diseases such as atherosclerosis, diabetes, and dementia.

Muscles of old laboratory rodents experience exaggerated force losses after eccentric contractile activity. We extended this line of inquiry to humans and investigated the influence of fiber myosin heavy chain (MHC) isoform content on the injury process. Skinned muscle fiber segments, prepared from vastus lateralis biopsies of elderly men and women (78 ± 2 years, N = 8), were subjected to a standardized eccentric contraction (strain, 0.25 fiber length; velocity, 0.50 unloaded shortening velocity). Injury was assessed by evaluating pre- and post-eccentric peak Ca2+-activated force per fiber cross-sectional area (Fmax). Over 90% of the variability in post-eccentric Fmax could be explained by a multiple linear regression model consisting of an MHC-independent slope, where injury was directly related to pre-eccentric Fmax, and MHC-dependent y-intercepts, where the susceptibility to injury could be described as type IIa/IIx fibers > type IIa fibers > type I fibers. We previously reported that fiber type susceptibility to the same standardized eccentric protocol was type IIa/IIx > type IIa = type I for vastus lateralis fibers of 25-year-old adults (Choi and Widrick, Am J Physiol Cell Physiol 299:C1409–C1417, 2010). Modeling combined data sets revealed significant age by fiber type interactions, with post-eccentric Fmax deficits greater for type IIa and type IIa/IIx fibers from elderly vs. young subjects at constant pre-eccentric Fmax. We conclude that the resistance of the myofilament lattice to mechanical strain has deteriorated for type IIa and type IIa/IIx, but not for type I, vastus lateralis fibers of elderly adults.

Hormones are potent mediators of developmental programming and maternal epigenetic effects. In vertebrates, developmental exposure to maternal androgen hormones has been shown to impact multiple behavioral and physiological traits of progeny, but the possible consequences of this early exposure in terms of aging-related changes in mortality and fitness remain largely unexplored. Avian eggs naturally contain variable doses of maternal hormones—in particular, androgens—which have documented effects on embryo growth and differentiation as well as adult behavior and physiology. Here, we report that injections of a physiological dose of testosterone (T) into yolks of freshly laid eggs of a small, seasonally breeding songbird, the house sparrow (Passer domesticus), increased survivorship in a semi-natural aviary environment. In addition, survival effects of developmental T exposure were sex-dependent, with males generally having a higher risk of death. Separate analyses for young birds in their first year of life (from hatching up to the first reproductive period the following calendar year) and in adulthood (after the first breeding season) showed similar effects. For first-year birds, mortality risk was higher during the winter than during the period after fledging; for adults, mortality risk was higher during the reproductive than the non-reproductive phase (post-breeding molt and winter). T treatment did not affect nestling body mass, but resulted in higher body mass at 3–4 months of age; T and body mass at this age interacted to influence mortality risk. Embryonic exposure to maternal testosterone may result in lower adult mortality by modifying intrinsic physiological processes involved in health or aging over the lifespan of adult birds.

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The executive function deficit is greater in depressed patients with cardiovascular disease than in depressed patients without cardiovascular disease. Late-life depression is said to have a vascular etiology and would worsen the executive function. A cross-sectional design was used for this study. The study was done in outpatient clinics of Kaohsiung Veterans General Hospital and National Cheng Kung University Hospital, Taiwan. Three hundred thirty-five older elderly men (>75 years old) were chosen as study participants, some military veterans and some not. The mini-mental state examination was used to exclude those suspected of dementia, the Mini-International Neuropsychiatric Interview to screen those undergoing a current major depressive episode, and the revised Geriatric Depression Scale Short Form to measure the severity of depression. Specialist physicians obtained past histories of medical illnesses through chart reviews, history taking, and health examinations. Elderly men with major depression comorbid with cardiovascular disease had worse executive functions. Executive function impairment is greater in elderly men diagnosed with major depression comorbid with cardiovascular disease than in those without cardiovascular disease.

Adenosine monophosphate-activated protein kinase (AMPK) is an evolutionary conserved energy sensor sensitive to changes in cellular AMP/ATP ratio which is activated by phosphorylation (pAMPK). pAMPK levels decrease in peripheral tissues with age, but whether this also occurs in the aged brain, and how this contributes to the ability of the aged brain to cope with ischemic stress is unknown. This study investigated the activation of AMPK and the response to AMPK inhibition after induced stroke in both young and aged male mice. Baseline levels of phosphorylated AMPK were higher in aged brains compared to young mice. Stroke-induced a robust activation of AMPK in young mice, yet this response was muted in the aged brain. Young mice had larger infarct volumes compared with aged animals; however, more severe behavioral deficits and higher mortality were seen in aged mice after stroke. Inhibition of AMPK with Compound C decreased infarct size in young animals, but had no effect in aged mice. Compound C administration led to a reduction in brain ATP levels and induced hypothermia, which led to enhanced neuroprotection in young but not aged mice. This work demonstrates that aging increases baseline brain pAMPK levels; aged mice have a muted stroke-induced pAMPK response; and that AMPK inhibition and hypothermia are less efficacious neuroprotective agents in the aged brain. This has important translational relevance for the development of neuroprotective agents in preclinical models and our understanding of the enhanced metabolic stress experienced by the aged brain.

Chronological lifespan (CLS) is defined as the duration of quiescence in which normal cells retain the capacity to reenter the proliferative cycle. This study investigates whether hydroxytyrosol (HT), a naturally occurring polyphenol found in olives, extends CLS in normal human fibroblasts (NHFs). Quiescent NHFs cultured for a long duration (30–60 days) lose their capacity to repopulate. Approximately 60% of these cells exit the cell cycle permanently; a significant increase in the doubling time of the cell population was observed. CLS was extended in quiescent NHFs that were cultured in the presence of HT for 30–60 days. HT-induced extension of CLS was associated with an approximately 3-fold increase in manganese superoxide dismutase (MnSOD) activity while there was no change in copper–zinc superoxide dismutase, catalase, or glutathione peroxidase protein levels. Quiescent NHFs overexpressing a dominant-negative mutant form of MnSOD failed to extend CLS. HT suppressed age-associated increase in mitochondrial ROS levels. Results from spectroscopy assays indicate that HT in the presence of peroxidases can undergo catechol–semiquinone–quinone redox cycling generating superoxide, which in a cellular context can activate the antioxidant system, e.g., MnSOD expression. These results demonstrate that HT extends CLS by increasing MnSOD activity and decreasing age-associated mitochondrial reactive oxygen species accumulation.

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Aging is associated with alterations in the intestinal microbiota and with immunosenescence. Probiotics have the potential to modify a selected part of the intestinal microbiota as well as improve immune functions and may, therefore, be particularly beneficial to elderly consumers. In this randomized, controlled cross-over clinical trial, we assessed the effects of a probiotic cheese containing Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus NCFM on the intestinal microbiota and fecal immune markers of 31 elderly volunteers and compared these effects with the administration of the same cheese without probiotics. The probiotic cheese was found to increase the number of L. rhamnosus and L. acidophilus NCFM in the feces, suggesting the survival of the strains during the gastrointestinal transit. Importantly, probiotic cheese administration was associated with a trend towards lower counts of Clostridium difficile in the elderly, as compared with the run-in period with the plain cheese. The effect was statistically significant in the subpopulation of the elderly who harbored C. difficile at the start of the study. The probiotic cheese was not found to significantly alter the levels of the major microbial groups, suggesting that the microbial changes conferred by the probiotic cheese were limited to specific bacterial groups. Despite that the administration of the probiotic cheese to the study population has earlier been shown to significantly improve the innate immunity of the elders, we did not observe measurable changes in the fecal immune IgA concentrations. No increase in fecal calprotectin and β-defensin concentrations suggests that the probiotic treatment did not affect intestinal inflammatory markers. In conclusion, the administration of probiotic cheese containing L. rhamnosus HN001 and L. acidophilus NCFM, was associated with specific changes in the intestinal microbiota, mainly affecting specific subpopulations of intestinal lactobacilli and C. difficile, but did not have significant effects on the major microbial groups or the fecal immune markers.

In the last decades, the participation of elderly trained people in endurance events such as marathon running has dramatically increased. Previous studies suggested that the performance of master runners (> 40 yrs) during marathon running has improved. The aims of the study were : (i) to analyze the changes in participation and performance trends of master marathon runners between 1980 and 2009 and, ii) to compare the gender differences in performance as a function of age across the years. Running times of the best male and female runners between 20 and 79 yrs of age who competed in the New-York City marathon were analyzed. Gender differences in performance times were analysed for the top 10 male and female runners between 20 and 65 yrs of age. The participation of master runners increased during the 1980–2009 period, to a greater extent for females compared to males. During that period, running times of master runners significantly (P<0.01) decreased for males older than 64 yrs and for females older than 44 yrs, respectively. Gender differences in running times decreased over the last 3 decades but remained relatively stable across the ages during the last decade. These data suggest that male (≥ 65 yrs) and female (≥ 45 yrs) master runners have probably not yet reached their limits in marathon performance. The relative stability of gender differences in marathon running times across the different age groups over the last decade also suggests that age-related declines in physiological function do not differ between male and female marathoners.