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Traveling to high-altitude destinations is associated with risks such as high-altitude sicknesses and impaired sleep and performance. Although antioxidant supplementation may be beneficial, conflicting study results impede clear clinical guidelines. Herein, we highlight the potential of the antioxidant compound melatonin that is surprisingly poorly investigated in high-altitude settings.

Elite masters endurance athletes are considered models of optimal healthy aging due to the maintenance of high cardiorespiratory fitness (CRF) until old age. Whereas a drop in VO2max in masters athletes has been broadly investigated, the modifying impact of training still remains a matter of debate. Longitudinal observations in masters endurance athletes demonstrated VO2max declines between −5% and −46% per decade that were closely related to changes in training volume. Here, using regression analyses, we show that 54% and 39% of the variance in observed VO2max decline in male and female athletes, respectively is explained by changes in training volume. An almost linear VO2max decrease was observed in studies on young and older athletes, as well as non-athletes, starting a few days after training cessation, with a decline of as much as −20% after 12 weeks. Besides a decline in stroke volume and cardiac output, training cessation was accompanied by considerable reductions in citrate synthase and succinate dehydrogenase activity (reduction in mitochondrial content and oxidative capacity). This reduction could largely be rescued within similar time periods of training (re)uptake. It is evident that training reduction or cessation leads to a considerably accelerated VO2max drop, as compared to the gradual aging-related VO2max decline, which can rapidly nullify many of the benefits of preceding long-term training efforts.

Living longer is associated with an increased risk of chronic diseases, including impairments of the musculoskeletal and immune system as well as metabolic disorders and certain cancers, each of which can negatively affect the relationship between host and microbiota up to the occurrence of dysbiosis. On the other hand, lifestyle factors, including regular physical exercise and a healthy diet, can affect skeletal muscle and immune aging positively at all ages. Accordingly, health benefits could partly depend on the effect of such interventions that influence the biodiversity and functionality of intestinal microbiota. In the present review, we first discuss the physiological effects of aging on the gut microbiota, immune system, and skeletal muscle. Secondly, we describe human epidemiological evidence about the associations between physical activity and fitness and the gut microbiota composition in older adults. The third part highlights the relevance and restorative mechanisms of immune protection through physical activity and specific exercise interventions during aging. Fourth, we present important research findings on the effects of exercise and protein as well as other nutrients on skeletal muscle performance in older adults. Finally, we provide nutritional recommendations to prevent malnutrition and support healthy active aging with a focus on gut microbiota. Key nutrition-related concerns include the need for adequate energy and protein intake for preventing low muscle mass and a higher demand for specific nutrients (e.g., dietary fiber, polyphenols and polyunsaturated fatty acids) that can modify the composition, diversity, and metabolic capacity of the gut microbiota, and may thus provide a practical means of enhancing gut and systemic immune function.

Muscle atrophy is an unfortunate effect of aging and many diseases and can compromise physical function and impair vital metabolic processes. Low levels of muscular fitness together with insufficient dietary intake are major risk factors for illness and mortality from all causes. Ultimately, muscle wasting contributes significantly to weakness, disability, increased hospitalization, immobility, and loss of independence. However, the extent of muscle wasting differs greatly between individuals due to differences in the aging process per se as well as physical activity levels. Interventions for sarcopenia include exercise and nutrition because both have a positive impact on protein anabolism but also enhance other aspects that contribute to well-being in sarcopenic older adults, such as physical function, quality of life, and anti-inflammatory state. The process of aging is accompanied by chronic immune activation, and sarcopenia may represent a consequence of a counter-regulatory strategy of the immune system. Thereby, the kynurenine pathway is induced, and elevation in the ratio of kynurenine to tryptophan concentrations, which estimates the tryptophan breakdown rate, is often linked with inflammatory conditions and neuropsychiatric symptoms. A combined exercise program consisting of both resistance-type and endurance-type exercise may best help to ameliorate the loss of skeletal muscle mass and function, to prevent muscle aging comorbidities, and to improve physical performance and quality of life. In addition, the use of dietary protein supplementation can further augment protein anabolism but can also contribute to a more active lifestyle, thereby supporting well-being and active aging in the older population.

Allergic diseases such as asthma and rhinitis, as well the early phase of atopic dermatitis, are characterized by a Th2-skewed immune environment. Th2-type cytokines are upregulated in allergic inflammation, whereas there is downregulation of the Th1-type immune response and related cytokines, such as interferon-γ (IFN-γ). The latter is a strong inducer of indoleamine 2,3-dioxygenase-1 (IDO-1), which degrades the essential amino acid tryptophan, as part of an antiproliferative strategy of immunocompetent cells to halt the growth of infected and malignant cells, and also of T cells - an immunoregulatory intervention to avoid overactivation of the immune system. Raised serum tryptophan concentrations have been reported in patients with pollen allergy compared to healthy blood donors. Moreover, higher baseline tryptophan concentrations have been associated with a poor response to specific immunotherapy. It has been shown that the increase in tryptophan concentrations in patients with pollen allergy only exists outside the pollen season, and not during the season. Interestingly, there is only a minor alteration of the kynurenine to tryptophan ratio (Kyn/Trp, an index of tryptophan breakdown). The reason for the higher tryptophan concentrations in patients with pollen allergy outside the season remains a matter of discussion. To this regard, the specific interaction of nitric oxide (NO∙) with the tryptophan-degrading enzyme IDO-1 could be important, because an enhanced formation of NO∙ has been reported in patients with asthma and allergic rhinitis. Importantly, NO∙ suppresses the activity of the heme enzyme IDO-1, which could explain the higher tryptophan levels. Thus, inhibitors of inducible NO∙ synthase should be reconsidered as candidates for antiallergic therapy out of season that may abrogate the arrest of IDO-1 by decreasing the production of NO∙. Considering its association with the pathophysiology of atopic disease, tryptophan metabolism may play a relevant role in the pathophysiology of allergic disorders.

With increasing age, the immune system undergoes a remodeling process, termed immunosenescence, which is accompanied by considerable shifts in leukocyte subpopulations and a decline in various immune cell functions. Clinically, immunosenescence is characterized by increased susceptibility to infections, a more frequent reactivation of latent viruses, decreased vaccine efficacy, and an increased prevalence of autoimmunity and cancer. Physiologically, the immune system has some adaptive strategies to cope with aging, while in some settings, maladaptive responses aggravate the speed of aging and morbidity. While a lack of physical activity, decreased muscle mass, and poor nutritional status facilitate immunosenescence and inflammaging, lifestyle factors such as exercise and dietary habits affect immune aging positively. This review will discuss the relevance and mechanisms of immunoprotection through physical activity and specific exercise interventions. In the second part, we will focus on the effect of dietary interventions through the supplementation of the essential amino acid tryptophan, n-3 polyunsaturated fatty acids, and probiotics (with a special focus on the kynurenine pathway).

Objective: To examine the association between grip strength and history of falls among older individuals, and to assess the possible mediating effect of balance problems on this relationship. Method: Data originate from KORA (Cooperative Health Research in the Region of Augsburg)-Age Study of 808 individuals (65 years and above). Follow-up assessment occurred 3 years later. Results: The risk of falls within the last 12 months was reduced on average by 3% (odds ratio [OR] 95% confidence interval [95% CI] = 0.97 [0.94, 0.99]; p value = .026) per 1-kg increase in maximum grip strength after adjusting for age and gender. There was a trend toward an indirect effect of grip strength through the mediator variable balance problems ( p value = .043). Discussion: Increased muscular strength is associated with a reduced risk of falls in older age after adjustment for age and gender. The association is partially mediated by balance problems. Thus, in older adults, muscle-strengthening exercises may decrease the risk of falling.

Background Frailty is a multidimensional syndrome correlated to the loss of homeostasis and increased vulnerability to stressors, which is associated with increase in the risk of disability, comorbidity, hospitalization, and death in the elderly. It is based on the interplay of physiological, psychological, social, and environmental factors. Objectives Because aging involves a detrimental immune response, this work aimed to assess the possible role of chronic low-grade immune stimulation on frailty status in the elderly. Methods Biomarkers involved in indoleamine 2,3-dioxygenase 1 and guanosine triphosphate cyclohydrolase I enzymatic pathways (namely neopterin, tryptophan, kynurenine, phenylalanine, tyrosine, and nitrite) were analyzed in a population of Spanish older adults aged 65 years and above, and their relationships with frailty status were evaluated. Results Significant increases in neopterin levels, kynurenine/tryptophan ratio, and phenylalanine/tyrosine ratio, and significant decreases in tryptophan, nitrite and tyrosine concentrations in frail individuals compared with nonfrail persons were obtained. Significant correlations were also observed between immune biomarkers, indicating they change in parallel, thus, pointing to interrelated causes. Besides, reference ranges for a number of immune biomarkers in the population of robust older adults were established for the first time. Conclusions Results obtained in the present study are consistent with the idea that frailty status in the elderly is associated with an additional degree of immune stimulation, manifested in a more intense disturbance of indoleamine 2,3-dioxygenase 1 and guanosine triphosphate cyclohydrolase I pathways than in nonfrail or prefrail older adults.

3rd International Conference on Occupational & Environmental Toxicology/3rd Ibero-American Meeting on Toxicology and Environmental Health International, 21-23 June 2016, Porto, Portugal [Abstract] Aging is associated with a decline in the normal functioning of the immune system. Several studies described the relationship between immunological alterations, including immunosenescence and inflammation, and aging or age-related outcomes, such as sarcopenia, depression, and neurodegenerative disorders. Physical activity is known to improve muscle function and to exert a number of benefits on older adult health, including reduced risk for heart and metabolic system chronic diseases. However, the positive influence of physical activity on the immune system has not been elucidated. In order to shed light on the role of physical activity in immune responses of older individuals, a number of immunological parameters comprising % lymphocyte subsets (CD3+, CD4+, CD8+, CD19+, and CD16+56+) and serum levels of neopterin and tryptophan metabolism products were evaluated in peripheral blood samples of older adults performing normal (N = 170) or reduced (N = 89) physical activity. In addition, the potential influence of other clinical and epidemiological factors was also considered. Results showed that subjects with reduced physical activity displayed significantly higher levels of CD4+/CD8+ ratio, kynurenine/tryptophan ratio, and serum neopterin, along with lower %CD19+ cells and tryptophan concentrations. Further, some immunological biomarkers were associated with cognitive impairment and functional status. These data contribute to reinforce the postulation that physical activity supports healthy aging, particularly by helping to protect the immunological system from aging-related changes. Xunta de Galicia; ED431B 2016/013 Xunta de Galicia; GPC2014/082

Background Reduced muscular strength in the old age is strongly related to activity impairment and mortality. However, studies evaluating the gender-specific association between muscularity and mortality among older adults are lacking. Thus, the objective of the present study was to examine gender differences in the association between muscular strength and mortality in a prospective population-based cohort study. Methods Data used in this study derived from the Cooperative Health Research in the Region of Augsburg (KORA)-Age Study. The present analysis includes 1,066 individuals (mean age 76 ± 11 SD years) followed up over 3years. Handgrip strength was measured using the Jamar Dynamometer. A Cox proportional hazard model was used to determine adjusted hazard ratios of mortality with 95% confidence intervals (95% CI) for handgrip strength. Potential confounders (i.e. age, nutritional status, number of prescribed drugs, diseases and level of physical activity) were pre-selected according to evidence-based information. Results During the follow-up period, 56 men (11%) and 39 women (7%) died. Age-adjusted mortality rates per 1,000 person years (95% CI) were 77 (59–106), 24 (13–41) and 14 (7–30) for men and 57 (39–81), 14 (7–27) and 1 (0–19) for women for the first, second and third sex-specific tertile of muscular strength, respectively. Low handgrip strength was significantly associated with all-cause mortality among older men and women from the general population after controlling for significant confounders. Hazard ratios (95% CI) comparing the first and second tertile to the third tertle were 3.33 (1.53–7.22) and 1.42 (0.61-3.28), respectively. Respective hazard ratios (95% CI) for mortality were higher in women than in men ((5.23 (0.67–40.91) and 2.17 (0.27–17.68) versus 2.36 (0.97–5.75) and 0.97 (0.36–2.57)). Conclusions Grip strength is inversely associated with mortality risk in older adults, and this association is independent of age, nutritional status, number of prescribed drugs, number of chronic diseases and level of physical activity. The association between muscular strength and all-cause mortality tended to be stronger in women. It seems to be particularly important for the weakest to enhance their levels of muscular strength in order to reduce the risk of dying early. &nbsp

Background: Prolonged intense exercise has been associated with transient suppression of immune function and an increased risk of infections. In this context, the catabolism of amino acid tryptophan via kynurenine may play an important role. The present study examined the effect of a probiotic supplement on the incidence of upper respiratory tract infections (URTI) and the metabolism of aromatic amino acids after exhaustive aerobic exercise in trained athletes during three months of winter training. Methods: Thirty-three highly trained individuals were randomly assigned to probiotic (PRO, n = 17) or placebo (PLA, n = 16) groups using double blind procedures, receiving either 1 × 1010 colony forming units (CFU) of a multi-species probiotic (Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Enterococcus faecium W54, Lactobacillus acidophilus W22, Lactobacillus brevis W63, and Lactococcus lactis W58) or placebo once per day for 12 weeks. The serum concentrations of tryptophan, phenylalanine and their primary catabolites kynurenine and tyrosine, as well as the concentration of the immune activation marker neopterin were determined at baseline and after 12 weeks, both at rest and immediately after exercise. Participants completed a daily diary to identify any infectious symptoms. Results: After 12 weeks of treatment, post-exercise tryptophan levels were lowered by 11% (a significant change) in the PLA group compared to the concentrations measured before the intervention (p = 0.02), but remained unchanged in the PRO group. The ratio of subjects taking the placebo who experienced one or more URTI symptoms was increased 2.2-fold compared to those on probiotics (PLA 0.79, PRO 0.35; p = 0.02). Conclusion: Data indicate reduced exercise-induced tryptophan degradation rates in the PRO group. Daily supplementation with probiotics limited exercise-induced drops in tryptophan levels and reduced the incidence of URTI, however, did not benefit athletic performance.

The prevalence of type 2 diabetes (T2D) is rapidly increasing, and effective strategies to manage and prevent this disease are urgently needed. Resistance training (RT) promotes health benefits through increased skeletal muscle mass and qualitative adaptations, such as enhanced glucose transport and mitochondrial oxidative capacity. In particular, mitochondrial adaptations triggered by RT provide evidence for this type of exercise as a feasible lifestyle recommendation to combat T2D, a disease typically characterized by altered muscle mitochondrial function. Recently, the synergistic and antagonistic effects of combined training and Metformin use have come into question and warrant more in-depth prospective investigations. In the future, clinical intervention studies should elucidate the mechanisms driving RT-mitigated mitochondrial adaptations in muscle and their link to improvements in glycemic control, cholesterol metabolism and other cardiovascular disease risk factors in individuals with T2D.

STRASSER, B., K. STEINDORF, J. WISKEMANN, and C. M. ULRICH. Impact of Resistance Training in Cancer Survivors: A MetaAnalysis. Med. Sci. Sports Exerc., Vol. 45, No. 11, pp. 2080–2090, 2013. Purpose: Current evidence suggests many health benefits from physical activity during and after cancer treatment. However, the optimal exercise program for cancer survivors has not yet been established. The purpose of this meta-analysis was to summarize evidence for the efficacy of resistance training (RT) interventions to improve muscle strength and body composition among adult cancer survivors. We also investigate potential dose–response relationships between intensity, duration, and frequency of RT and assessed outcomes. Methods: A systematic literature review of the Clinical Trial Register, Cochrane Trial Register, MEDLINE, and EMBASE literature databases was undertaken. Studies were included if they were randomized controlled trials (RCT) comparing RT with an exercise or nonexercise control group in cancer survivors during and after treatment. Thirteen articles from 11 RCT met our inclusion criteria. We performed a random-effects meta-analysis to determine weighted mean differences (WMD) with 95% confidence intervals using the Cochrane Review Manager 5.0.25. A random-effects metaregression model was performed to examine dose–response relationships between RT variables and assessed outcomes. Results: Quantitative evidence shows a large effect of RT on lower-limb and upper-limb muscle strength (WMD: +14.57 kg, P = 0.0005 and +6.90 kg, P G 0.00001, respectively) and moderate effects on lean body mass and percentage of body fat (WMD: +1.07 kg, P G 0.0001 and j2.08%, P = 0.003, respectively). A small positive effect of RT was noted on Functional Assessment of Cancer Therapy–Fatigue (P = 0.05). Upper-limb muscle strength and percentage of body fat improved to a greater extent when RT interventions were of low to moderate intensity (e75% one-repetition maximum, P = 0.042). Conclusions: RT was shown to be associated with clinically important positive effects on

Type 2 diabetes mellitus (T2D) is characterized by insulin resistance, impaired glycogen synthesis, lipid accumulation, and impaired mitochondrial function. Exercise training has received increasing recognition as a cornerstone in the prevention and treatment of T2D. Emerging research suggests that resistance training (RT) has the power to combat metabolic dysfunction in patients with T2D and seems to be an effective measure to improve overall metabolic health and reduce metabolic risk factors in diabetic patients. However, there is limited mechanistic insight into how these adaptations occur. This review provides an overview of the intervention data on the impact of RT on glucose metabolism. In addition, the molecular mechanisms that lead to adaptation in skeletal muscle in response to RT and that are associated with possible beneficial metabolic responses are discussed. Some of the beneficial adaptations exerted by RT include increased GLUT4 translocation in skeletal muscle, increased insulin sensitivity and hence restored metabolic flexibility. Increased energy expenditure and excess postexercise oxygen consumption in response to RT may be other beneficial effects. RT is increasingly establishing itself as an effective measure to improve overall metabolic health and reduce metabolic risk factors in diabetic patients.

Exhaustive exercise can cause a transient depression of immune function. Data indicate significant effects of immune activation cascades on the biochemistry of monoamines and amino acids such as tryptophan. Tryptophan can be metabolized through different pathways, a major route being the kynurenine pathway, which is often systemically up-regulated when the immune response is activated. The present study was undertaken to examine the effect of exhaustive aerobic exercise on biomarkers of immune activation and tryptophan metabolism in trained athletes. After a standardized breakfast 2 h prior to exercise, 33 trained athletes (17 women, 16 men) performed an incremental cycle ergometer exercise test at 60 rpm until exhaustion. After a 20 min rest phase, the participants performed a 20 min maximal time-trial on a cycle ergometer (RBM Cyclus 2, Germany). During the test, cyclists were strongly encouraged to choose a maximal pedalling rate that could be maintained for the respective test duration. Serum concentrations of amino acids tryptophan, kynurenine, phenylalanine, and tyrosine were determined by HPLC and immune system biomarker neopterin by ELISA at rest and immediately post exercise. Intense exercise was associated with a strong increase in neopterin concentrations (p

An association between mood disturbance, the inability to lose or to stop gaining weight, and a craving for carbohydrates is manifested by many people who are overweight or are becoming so. In a recent study, we observed that low-calorie weight loss diet lowered not only levels of lept in but also levels of essential amino acid tryptophan (TRP) significantly. The disturbed metabolism of TRP might affect biosynthesis of serotonin and could thereby increase the susceptibility for mood disturbances and carbohydrate craving, increasing the cessation probability of weight reduction programs. Alternatively, moderate physical exercise – a potent stimulus to modulate (reduce/normalize) proinflammatory cytokines, which may affect TRP levels – could be helpful in improving mood status and preventing uncontrolled weight gain. In contrast, excessive physical exercise may induce breakdown of TRP when proinflammatory cascades together with TRP-degrading enzyme indoleamine 2,3-dioxygenase-1 are stimulated, which may lead to neuropsychiatric symptoms such as fatigue and low mood.

Background/Aims: In 2008, the American Diabetes Association recommended low-carbohydrate or low-fat diets for weight management in patients with established type 2 diabetes (T2D), while the amount of monounsaturated fatty acids (MUFA) was not specified. This systematic review focused on the effects of diets high in MUFA versus diets low in MUFA on important risk factors of T2D (i.e. plasma glucose, insulin, homeostasis model assessment of insulin resistance and glycosylated haemoglobin, HbA1c). Methods: Nine randomized controlled intervention trials with a total of 1,547 participants and a running time of at least 6 months, comparing diets high versus low in MUFA among adults with abnormal glucose metabolism (T2D, impaired glucose tolerance and insulin resistant), being overweight or obese, have been included in the meta-analysis. We performed a random effects meta-analysis to determine the weighted mean differences with 95% confidence intervals using the software package Review Manager 5.0.25 of the Cochrane Collaboration. Results: Significant differences in HbA1c were found (weighted mean difference –0.21%, 95% CI –0.40 to –0.02; p = 0.03), favouring the high MUFA groups. In contrast, fasting plasma glucose, fasting plasma insulin as well as the homeostasis model assessment of insulin resistance were not affected by the amounts of MUFA in the dietary protocols. Conclusions: In summary, this systematic review found that high MUFA diets appear to be effective in reducing HbA1c, and therefore, should be recommended in the dietary regimes of T2D.

Over the last decade, investigators have paid increasing attention to the effects of resistance training (RT) on several metabolic syndrome variables. Evidence suggests that skeletal muscle is responsible for up to 40% of individuals' total body weight and may be influential in modifying metabolic risk factors via muscle mass development. Due to the metabolic consequences of reduced muscle mass, it is understood that normal aging and/or decreased physical activity may lead to a higher prevalence of metabolic disorders. The purpose of this review is to (1) evaluate the potential clinical effectiveness and biological mechanisms of RT in the treatment of obesity and (2) provide up-to-date evidence relating to the impact of RT in reducing major cardiovascular disease risk factors (including dyslipidaemia and type 2 diabetes). A further aim of this paper is to provide clinicians with recommendations for facilitating the use of RT as therapy in obesity and obesity-related metabolic disorders.

It was the Summer Olympic Games 1968 held in Mexico City (2,300 m) that required scientists and coaches to cope with the expected decline of performance in endurance athletes and to establish optimal preparation programs for competing at altitude. From that period until now many different recommendations for altitude acclimatization in advance of an altitude competition were proposed, ranging from several hours to several weeks. Those recommendations are mostly based on the separate consideration of the physiology of acclimatization, psychological issues, performance changes, logistical or individual aspects, but there is no review considering all these aspects in their entirety. Therefore, the present work primarily focusses on the period of altitude sojourn prior to the competition at altitude based on physiological and psychological aspects complemented by nutritional and sports practical considerations.