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Bariatric surgery (BS) is effective in improving chronic joint pain (CJP). However, the long-term effects on this comorbidity are poorly understood.To determine the prevalence of CJP in a sample of patients who had undergone BS with a minimum follow-up of 18 months. To determine whether or not there was any relationship between CJP and clinical or psychological outcomes after BS.Cross-sectional study. The Lattinen index (LI) was used to evaluate CJP, using the cut-off point of 10 to define significant CJP (SCJP).Of the 110 subjects assessed, 31.2% (35/110) had SCJP. The patients with SCJP were older (57.4±13 vs 47.8±11.6 years; p0.0001) and more time had elapsed since their BS (105.6±54.3 vs 78.5±39 months; p=0.023). The last BMI was higher in subjects with SCJP (35±5 vs 33.3±6.9kg/mSCJP is highly prevalent in patients who have had BS once they reach the weight plateau phase. There is an association between having SCJP and worse psychological and functional status, with potential detrimental metabolic effects.

Background: We wanted to assess the prevalence of individuals with food addiction (FA) among bariatric surgery (BS) patients at long term and to determine if there was any relationship between FA a...

Demographic aging is one of the most serious challenges facing our society. Although we live longer, we do not live better because it is considered that approximately 16–20% of our life is spent in late-life morbidity. Older people have the greatest risk of developing frailty increasing the risk of presenting various adverse health events such as low quality of life, disability, hospitalization and even death. Frail men and women over 65 years old have lower muscle quality and muscle mass and higher percentage of body fat than non-frail people of the same age. In this review we will address the main physiological changes in the muscular and nervous system associated to aging. More specifically we will review the changes in muscle mass, quality, and strength relating them with the decrease in capillarization and muscular oxidative capacity as well as with the alterations in protein synthesis in the muscle with aging. The last section of the manuscript will be devoted to the animal models of frailty and the indexes developed to measure frailty in these models. We will finally address the importance of exercise training as an intervention to delay or even reverse frailty. Keywords: Sarcopenia, Multicomponent exercise, Disability, Skeletal muscle, Healthy aging

Background: Frailty is a major age-associated syndrome leading to disability. Oxidative damage plays a significant role in the promotion of frailty. The cellular antioxidant system relies on reduced nicotinamide adenine dinucleotide phosphate (NADPH) that is highly dependent on glucose 6-P dehydrogenase (G6PD). The G6PD-overexpressing mouse (G6PD-Tg) is protected against metabolic stresses. Our aim was to examine whether this protection delays frailty. Methods: Old wild-type (WT) and G6PD-Tg mice were evaluated longitudinally in terms of frailty. Indirect calorimetry, transcriptomic profile, and different skeletal muscle quality markers and muscle regenerative capacity were also investigated. Results: The percentage of frail mice was significantly lower in the G6PD-Tg than in the WT genotype, especially in 26-month-old mice where 50% of the WT were frail vs. only 13% of the Tg ones (P < 0.001). Skeletal muscle transcriptomic analysis showed an up-regulation of respiratory chain and oxidative phosphorylation (P = 0.009) as well as glutathione metabolism (P = 0.035) pathways in the G6PD-Tg mice. Accordingly, the Tg animals exhibited an increase in reduced glutathione (34.5%, P < 0.01) and a decrease on its oxidized form (-69%, P < 0.05) and in lipid peroxidation (4-HNE: -20.5%, P < 0.05). The G6PD-Tg mice also showed reduced apoptosis (BAX/Bcl2: -25.5%, P < 0.05; and Bcl-xL: -20.5%, P < 0.05), lower levels of the intramuscular adipocyte marker FABP4 (-54.7%, P < 0.05), and increased markers of mitochondrial content (COX IV: 89.7%, P < 0.05; Grp75: 37.8%, P < 0.05) and mitochondrial OXPHOS complexes (CII: 81.25%, P < 0.01; CIII: 52.5%, P < 0.01; and CV: 37.2%, P < 0.05). Energy expenditure (-4.29%, P < 0.001) and the respiratory exchange ratio were lower (-13.4%, P < 0.0001) while the locomotor activity was higher (43.4%, P < 0.0001) in the 20-month-old Tg, indicating a major energetic advantage in these mice. Short-term exercise training in young C57BL76J mice induced a robust activation of G6PD in skeletal muscle (203.4%, P < 0.05), similar to that achieved in the G6PD-Tg mice (142.3%, P < 0.01). Conclusions: Glucose 6-P dehydrogenase deficiency can be an underestimated risk factor for several human pathologies and even frailty. By overexpressing G6PD, we provide the first molecular model of robustness. Because G6PD is regulated by pharmacological and physiological interventions like exercise, our results provide molecular bases for interventions that by increasing G6PD will delay the onset of frailty. This work was supported by Instituto de Salud Carlos III CB16/10/00435 (CIBERFES) (PID2019-110906RB-I00/AEI/10.13039/501100011033) from the Spanish Ministry of Innovation and Science; 109_RESIFIT from Fundación General CSIC; PROMETEO/2019/097 de ‘Consellería, de Sanitat de la Generalitat Valenciana’ and EU Funded H2020-DIABFRAIL-LATAM (Ref: 825546); European Joint Programming Initiative ‘A Healthy Diet for a Healthy Life’ (JPI HDHL); and the ERA-NET Cofund ERA-HDHL (GA No. 696295 of the EU Horizon 2020 Research and Innovation Programme). Part of the equipment employed in this work has been funded by Generalitat Valenciana and co-financed with ERDF funds (OP ERDF of Comunitat Valenciana 2014–2020). Work in the laboratory of P.J.F.-M. was funded by the FBBVA and the Ramón Areces Foundations. Work in the laboratory of P.M.-C. and A.L.S was funded by by MWRF and Fundació La Marató/TV3-80/19-202021 to P.M.C. and Fundació La Marató de TV3 (Project 202033 to A.L.S.), MINECO-Spain (RTI2018-096068), ERC-2016-AdG-741966, LaCaixa-HEALTH-HR17-00040, MDA, UPGRADE-H2020-825825, AFM, and DPP-Spain; María-de-Maeztu-Program for Units of Excellence to UPF (MDM-2014-0370); and Severo-Ochoa-Program for Centers of Excellence to CNIC (SEV-2015-0505). A.S.-P. was supported by a fellowship from the Spanish ‘Ministerio de Educación, Cultura y Deporte’, award FPU 14/00098.

Highlights • Low levels of physical activity are a risk factor associated with Alzheimer's disease. • Older adults who exercise are more likely to maintain cognition. • Exercise modulates amyloid β turnover, inflammation, synthesis, and release of neurotrophins, and cerebral blood flow., Dementia is one of the greatest global challenges for health and social care in the 21st century. Alzheimer's disease (AD), the most common type of dementia, is by no means an inevitable consequence of growing old. Several lifestyle factors may increase, or reduce, an individual's risk of developing AD. Much has been written over the ages about the benefits of exercise and physical activity. Among the risk factors associated with AD is a low level of physical activity. The relationship between physical and mental health was established several years ago. In this review, we discuss the role of exercise (aerobic and resistance) training as a therapeutic strategy for the treatment and prevention of AD. Older adults who exercise are more likely to maintain cognition. We address the main protective mechanism on brain function modulated by physical exercise by examining both human and animal studies. We will pay especial attention to the potential role of exercise in the modulation of amyloid β turnover, inflammation, synthesis and release of neurotrophins, and improvements in cerebral blood flow. Promoting changes in lifestyle in presymptomatic and predementia disease stages may have the potential for delaying one-third of dementias worldwide. Multimodal interventions that include the adoption of an active lifestyle should be recommended for older populations.

Muscle mass and strength are very important for exercise performance. Training-induced musculoskeletal injuries usually require periods of complete immobilization to prevent any muscle contraction of the affected muscle groups. Disuse muscle wasting will likely affect every sport practitioner in his or her lifetime. Even short periods of disuse results in significant declines in muscle size, fiber cross sectional area, and strength. To understand the molecular signaling pathways involved in disuse muscle atrophy is of the utmost importance to develop more effective countermeasures in sport science research. We have divided our review in four different sections. In the first one we discuss the molecular mechanisms involved in muscle atrophy including the main protein synthesis and protein breakdown signaling pathways. In the second section of the review we deal with the main cellular, animal, and human atrophy models. The sources of reactive oxygen species in disuse muscle atrophy and the mechanism through which they regulate protein synthesis and proteolysis are reviewed in the third section of this review. The last section is devoted to the potential interventions to prevent muscle disuse atrophy with especial consideration to studies on which the levels of endogenous antioxidants enzymes or dietary antioxidants have been tested. Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

[ES] La historia del clarinete se ha visto influenciada principalmente por dos escuelas, las que a su vez estaban ligadas al diferente tipo de construcción del instrumento. Esta diferente forma constructiva del clarinete tuvo lugar en distintos momentos históricos y geográficos, pero sobretodo por las diferencias físicas en cuanto a las dimensiones internas del instrumento, colocación de las llaves y hoy en día en diferentes tipos del conjunto boquilla-lengüeta. Todo este tipo de particularidades, hizo que se diferenciaran dos tipos de instrumentos, el clarinete alemán y el clarinete francés. Las dos principales diferencias entre los dos instrumentos que encontramos se podrían enumerar en: ¿ Objetiva, la construcción del instrumento, colocación de las llaves, dimensiones del tubo. ¿ Subjetiva, la sonoridad emitida por el instrumento y la percepción sonora que tiene el oyente. Este trabajo pretende incidir en la posible relación que pueda existir entre la construcción del instrumento y el diferente tipo de sonoridad emitida por el instrumento y percibida por el oyente por cada uno de los dos sistemas constructivos, alemán y francés. El estudio constará de tres partes: 1) Marco teórico, con todos los conceptos relacionados con la acústic a del instrumento. 2) Marco práctico, con un estudio práctico comparativo y un estudio de percepción con cuestionarios de respuestas cerradas. 3) Conclusiones extraidas de las anteriores estrategias metodológicas., [EN] Two mainly schools influenced Clarinet's history due to different way of instrument's construction. This different constructive form of the clarinet took place in different historical and geographical moments, but above all because of the physical differences in the internal dimensions of the instrument, placing the keys and nowadays in different types of mouthpiece-reed assembly. All this type of peculiarities, made that two types of instruments were differentiated, the German clarinet and the French clarinet. The two main differences between the two instruments that we found could be listed in: - Objective, the construction of the instrument, placement of the keys, dimensions of the tube. - Subjective, the sonority emitted by the instrument and the sound perception of the listener. This work intends to affect the possible relationship that may exist between the construction of the instrument and the different type of sonority emitted by the instrument and perceived by the listener for each one of the two constructive systems, German and French. The study will consist of three parts: 1) theoretical framework, with all the concepts related to the acústic of the instrument. 2) practical framework, including both a practical study and a study of perception with questionnaires of closed answers. 3) Conclusions extracted from the previous methodological strategies.

Fasting is a component of many species' life history due to environmental factors or behavioral patterns that limit access to food. Despite metabolic and physiological challenges associated with these life history stages, fasting-adapted wild vertebrates exhibit few if any signs of oxidative stress, suggesting that fasting promotes redox homeostasis. Here we review mammalian, avian, reptilian, amphibian, and piscine examples of animals undergoing fasting during prolonged metabolic suppression (e.g. hibernation and estivation) or energetically demanding processes (e.g. migration and breeding) to better understand the mechanisms underlying fasting tolerance in wild vertebrates. These studies largely show beneficial effects of fasting on redox balance via limited oxidative damage. Though some species exhibit signs of oxidative stress due to energetically or metabolically extreme processes, fasting wild vertebrates largely buffer themselves from the negative consequences of oxidative damage through specific strategies such as elevating antioxidants, selectively maintaining redox balance in critical tissues, or modifying behavioral patterns. We conclude with suggestions for future research to better elucidate the protective effects of fasting on oxidative stress as well as disentangle the impacts from other life history stages. Further research in these areas will facilitate our understanding of the mechanisms wild vertebrates use to mitigate the negative impacts associated with metabolically-extreme life history stages as well as potential translation into therapeutic interventions in non-fasting-adapted species including humans.

Exercise causes an increase in the production of free radicals [1]. As a result of a hormetic mechanism antioxidant enzymes are synthesised and the cells are protected against further oxidative stress. Thus, exercise can be considered as an antioxidant [2]. Age-associated frailty is a major medical and social concern as it can easily lead to dependency. In this review we describe that oxidative stress is associated with frailty and the mechanism by which exercise prevents age-associated frailty. We propose that individually tailored multicomponent exercise programmes are one of the best ways to prevent and to treat age-associated frailty.

Frailty is associated with loss of functional reserve as well as with the prediction of adverse events in the old population. The traditional criteria of frailty are based on five physical determinations described in the Cardiovascular Health Study. We propose that biological and genetic markers of frailty should be used to increase the predictive capacity of the established clinical indeces. In recent times, research for biological markers of frailty has gained impetus. Finding a biological markers with diagnostic and prognostic capacity would be a major milestone to identify frailty risk, and also pre-frailty status. In the first section of the manuscript, we review the available biomarkers that help to monitor and prevent the evolution and the efficacy of interventions to delay the onset of frailty and to prevent its progression to incapacity. We also discuss the contribution of genetics to frailty. There are scientific bases that support that genetics influences frailty, although environmental factors probably will have the highest contribution. We review the known SNPs of the genes associated with frailty and classify them, taking into account the pathway in which they are involved. We also highlight the importance of longevity genes and their possible relation with frailty, citing centenarians who reach a very old age as an example of successful ageing. Finally, the reversibility of frailty is discussed. It can potentially be treated with nutritional or pharmacological interventions. However, physical exercise seems to be the most effective strategy to treat and prevent frailty. The last section of the manuscript is devoted to explaining the recommendations on the appropriate design of an exercise protocol to maximize its beneficial effects in a population of frail individuals.

Background Frailty can be an important clinical target to reduce rates of disability. Objective To ascertain if a supervised-facility multicomponent exercise program (MEP) when performed by frail older persons can reverse frailty and improve functionality; cognitive, emotional, and social networking; as well as biological biomarkers of frailty, when compared with a controlled population that received no training. Design This is an interventional, controlled, simple randomized study. Researchers responsible for data gathering were blinded for this study. Setting Participants from 2 primary rural care centers (Sollana and Carcaixent) of the same health department in Spain were enrolled in the study between December 2013 and September 2014. Patients We randomized a volunteer sample of 100 men and women who were sedentary, with a gait speed lower than 0.8 meters per second and frail (met at least 3 of the frailty phenotype criteria). Interventions Participants were randomized to a supervised-facility MEP (n = 51, age = 79.5, SD 3.9) that included proprioception, aerobic, strength, and stretching exercises for 65 minutes, 5 days per week, 24 weeks, or to a control group (n = 49, age = 80.3, SD 3.7). The intervention was performed by 8 experienced physiotherapists or nurses. Protein-calorie and vitamin D supplementation were controlled in both groups. Results Our MEP reverses frailty (number needed to treat to recover robustness in subjects with attendance to ≥50% of the training sessions was 3.2) and improves functional measurements: Barthel (trained group 91.6 SD 8.0 vs 82.0 SD 11.0 control group), Lawton and Brody (trained group 6.9 SD 0.9 vs 5.7 SD 2.0 control group), Tinetti (trained group 24.5 SD 4.4 vs 21.7 SD 4.5 control group), Short Physical Performance Battery (trained group 9.5 SD 1.8 vs 7.1 SD 2.8 control group), and physical performance test (trained group 23.5 SD 5.9 vs 16.5 SD 5.1 control group) as well as cognitive, emotional, and social networking determinations: Mini-Mental State Examination (trained group 28.9 SD 3.9 vs 25.9 SD 7.3 control group), geriatric depression scale from Yesavage (trained group 2.3 SD 2.2 vs 3.2 SD 2.0 control group), EuroQol quality-of-life scale (trained group 8.2 SD 1.6 vs 7.6 SD 1.3 control group), and Duke social support (trained group 48.5 SD 9.3 vs 41.2 SD 8.5 control group). This program is unique in that it leads to a decrease in the number of visits to primary care physician (trained group 1.3 SD 1.4 vs 2.4 SD 2.9 control group) and to a significant improvement in frailty biomarkers. Conclusions We have designed a multicomponent exercise intervention that reverses frailty and improves cognition, emotional, and social networking in a controlled population of community-dwelling frail older adults. Trial Registration ClinicalTrials.gov. Identifier: NCT02331459.

The beneficial effects of exercise have been well recognized for over half a century. Dr Jeremy Morris's pioneering studies in the fifties showed a striking difference in cardiovascular disease between the drivers and conductors on the double-decker buses in London. These studies sparked off a vast amount of research on the effects of exercise in health, and the general consensus is that exercise contributes to improved outcomes and treatment for several diseases including osteoporosis, diabetes, depression and atherosclerosis. Evidence of the beneficial effects of exercise is reviewed here. One way of highlighting the impact of exercise on disease is to consider it from the perspective of good practice. However, the intensity, duration, frequency (dosage) and counter indications of the exercise should be taken into consideration to individually tailor the exercise programme. An important case of the beneficial effect of exercise is that of ageing. Ageing is characterized by a loss of homeostatic mechanisms, on many occasions leading to the development of frailty, and hence frailty is one of the major geriatric syndromes and exercise is very useful to mitigate, or at least delay, it. Since exercise is so effective in reducing frailty, we would like to propose that exercise be considered as a supplement to other treatments. People all over the world have been taking nutritional supplements in the hopes of improving their health. We would like to think of exercise as a physiological supplement not only for treating diseases, but also for improving healthy ageing.

An enormous increment in the average lifespan of diverse populations occurred worldwide in the 20th century. In the last 10–15 years, the importance has changed from extending average and even maximal longevity to favoring healthy aging, and many researchers have focused their studies on the aim at extending healthspan. Prolonging lifespan without taking care of improving healthspan can derive in a long time of living with disabilities and constitutes a risk factor for the old population to suffer a higher prevalence of aging-related diseases. Indeed, modern disease treatments frequently diminish mortality without any effect on the deterioration of overall health. Understanding the mechanisms underlying the biology of aging allows the design of interventions and treatments oriented to diminish chronic diseases. Many theories agree in considering that the underlying cause of aging is the accumulation of molecular damage, which is originated principally by reactive oxygen species (ROS). In this regard, the free radical theory of aging postulated by Denham Harman in 1956, states that aging and the degenerative diseases associated with it are due to the progressive and irreversible accumulation of oxidative damage caused by ROS. The interventions aim at potentiating the antioxidant systems have acquired much relevance in the field, and it has been demonstrated that the overexpression of antioxidant enzymes in mice improves healthspan and, in some few cases, increases lifespan. Protection against oxidative damage largely relies on the reductive power of the molecule nicotinamide adenine dinucleotide phosphate in its reduced form (NAPDH), whose levels are mostly determined by the enzyme glucose-6-phosphate dehydrogenase (G6PD). Genetic manipulation is one of the mechanisms by which we can act on the levels of ROS in the organism. The general aim of this PhD thesis is to study in vivo the effect of G6PD moderate overexpression on oxidative stress parameters and on several indicators of organismal functionality declining with age, as well as to determine the effect of this genetic manipulation on the skeletal muscle regeneration capacity. This general objective is to be achieved using a transgenic mouse model with moderate ubiquitous overexpression of human G6PD under the control of its natural promoter (named as G6PD-Tg mice). The results show that G6PD-Tg mice present ~ 2-fold overexpression of G6PD mRNA, a similar increase in G6PD protein levels, and higher G6PD activity in the tissues examined. This overexpression is accompanied by an increase in NADPH levels, as well as higher plasma uric acid and lactate levels, indicating an activation of the PPP pathway. In addition, G6PD-Tg mice have lower levels of ROS-derived damage compared to their control littermates. In particular, females and males accumulate less oxidized DNA in the liver and brain, and females also display in the liver lower levels of lipid peroxidation as well as an increase in the GSH:GSSG ratio, due to higher GSH levels. All of this is accompanied by partial protection from aging-associated functional decline, including extended median lifespan in females, improved glucose tolerance and insulin sensitivity in males, and better neuromuscular fitness in females. However, skeletal muscle regeneration after cardiotoxin injury is not modified in young G6PD-Tg female mice. This genetic manipulation does not overstimulate protein synthesis. On the contrary, it induces a prooxidant environment, which might be attributed to the NADPH oxidase enzyme. The main conclusion of this PhD thesis is that moderate systemic overexpression of G6PD constitutes a beneficial intervention in mice for improving healthspan. This improvement is achieved through higher cellular NADPH levels and, as a consequence, better protection from the age-related ROS damage. This genetic manipulation neither improves or worsens skeletal muscle regeneration.