Effect of ß-alanine and sodium bicarbonate co-supplementation on the body's buffering capacity and sports performance: A systematic review.

Muscle acidification is one of the main factors causing fatigue during exercise, thus compromising performance. The sport supplements beta alanine (ß-A) and sodium bicarbonate (SB) are thought to enhance the effects of the body's buffer systems by reducing H+ concentrations. The aim of this systematic review was to analyze the effects of ß-A and SB co-supplementation on the organism's buffering capacity and sport performance. The databases PubMed, Web of Science, Medline, CINAHL and SPORTDiscus were searched until November 2021 following PRISMA guidelines. Randomized controlled trials, at least single-blind, performed in athletes of any age were considered. Nine studies including a total of 221 athletes were identified for review. Athletes were supplemented with ß-A and SB while they performed exercise tests to assess physical performance and buffer capacity. Five of the nine studies indicated there was some additional improvement in buffering capacity and performance with co-supplementation, while one study concluded that the effect was comparable to the added effects of the individual supplements. According to the results of the studies reviewed, we would recommend ß-A and SB co-supplementation during high intensity exercises lasting between 30 s and 10 min.

Muscle hypertrophy induced by N-3 PUFA supplementation in absence of exercise: a systematic review of randomized controlled trials.

The use of omega-3 polyunsaturated fatty acids (n-3 PUFA) has been studied in physically active population, however, there is a lack of information about the effects of n-3 PUFA supplementation on people with a sedentary behavior or who are undergoing a period of limb immobilization. This systematic review aims to examine the effect of n-3 PUFA on lean mass and muscle protein synthesis (MPS) in absence of physical training. The PubMed, Web of Science, MEDLINE, CINAHL and SPORTDiscus databases were searched following the PRISMA guidelines. Only randomized controlled trials, at least single blind, performed with sedentary humans were considered. Seven studies on a total of 192 individuals were included. Five of the six studies which measured changes in skeletal muscle volume and mass showed higher values with n-3 PUFA. Only two studies measured skeletal muscle protein expression. Both showed beneficial effects of supplementation in muscle protein fractional synthesis rate (FSR), while no effect of n-3 PUFA was observed for mechanistic target of rapamycin (mTOR) and kinase protein (Akt). In addition, ribosomal protein S6 kinase 1 (p70s6k) improved with n-3 PUFA only in one study. Finally, the two studies which measured the skeletal muscle gene expression observed no effect of supplementation.

Rhodiola rosea supplementation on sports performance: A systematic review of randomized controlled trials.

The aim of this systematic review was to determine whether the supplementation with Rhodiola rosea (RR), an herb that has been used for centuries for its various properties, can have an effect on muscle damage and physical performance. The databases PubMed, Web of Science, and Cochrane Library were used to find studies published until March 2023. Randomized controlled trials, healthy participants, and no use of other supplements. The search strategy was conducted by two independent reviewers, and specific information was extracted from the selected studies. Thirteen studies were included with 263 participants (198 men and 65 women between 18 and 65 years old). Two studies followed acute supplementation, 5 chronic, and 6 combined both. The results were heterogenous, having 11 studies with some positive effects, while 2 studies show no effect in variables such as rating of perceive exertion, heart rate, antioxidant capacity, blood lactate, creatine kinase, or C-reactive protein. Two limitations were found, firstly, the difference between supplementation and exercise protocols, and secondly, the existence of unclear or high risk of bias in most of the studies included. Acute supplementation with RR has a positive effect on endurance performance and rating of perceived exertion (RPE). Chronic supplementation has a positive effect on anaerobic exercise performance, but not endurance exercise performance. Chronic supplementation may positively impact muscle damage during exercise. However, more high-quality studies are needed to firmly establish the clinical efficacy of RR.

N-3 PUFA as an ergogenic supplement modulating muscle hypertrophy and strength: a systematic review.

There is growing evidence that suggests that n-3 polyunsaturated fatty acids (PUFA) may improve physical performance when combined with proper training through modulation of muscle hypertrophy, muscle strength, and delayed onset muscle soreness (DOMS). This systematic review aims to examine the effect and optimal dosage of n-3 PUFA supplementation on muscle hypertrophy, muscle strength, and DOMS when combined with physical exercise. The PubMed, Web of Science, MEDLINE Complete, CINAHL and SPORTDiscus databases were searched following the PRISMA guidelines. Randomized controlled trials performed with healthy humans were considered. Fifteen studies with a total of 461 individuals were included in this systematic review. All of them measured muscle function (short physical performance test, range of motion (ROM), electromechanical delay (EMD), muscle echo intensity or muscle quality) and DOMS. Fourteen studies evaluated muscle strength and only six assessed muscle hypertrophy. Our results demonstrated that n-3 PUFA does not improve muscle hypertrophy, muscle strength or skeletal muscle biomarkers of inflammation and muscle damage beyond the benefits obtained by the training itself. Nevertheless, n-3 PUFA improves DOMS recovery and muscle function (measured by ROM, EMD and muscle quality).

Synergy of carbohydrate and caffeine ingestion on physical performance and metabolic responses to exercise: A systematic review with meta-analysis.

Carbohydrates (CHO) and caffeine (CAF) are two ergogenic aids commonly used among athletes to enhance performance. However, there is some controversy as to whether the concurrent intake of both supplements might result in an additive and synergistic improvement in exercise performance. The aim of this systematic review and meta-analysis was to determine the effect of adding CAF to a protocol of CHO ingestion, compared with the intake of each ergogenic aid alone and with placebo, on exercise performance and metabolic responses in healthy young physically active adults. This study was conducted according to PRISMA 2020 guidelines. The PubMed, Web of Science, Medline Complete, CINAHL, SPORTDiscus and CENTRAL databases were searched including randomized controlled trials (RCT) that were at least single blind. The risk of bias assessment was performed using the Cochrane Risk-of-Bias tool 2. Meta-analysis were performed on performance variables and rating of perceived exertion (RPE) using the random-effects model. Thirteen RCT with 128 participants (117 men and 11 women) were included in this study. The ingestion of CAF and CHO reduced sprint time during repeated sprint protocols in comparison with CHO isolated ingestion (SMD: -0.45; 95% CI: -0.85, -0.05) while there was a tendency for a reduction in the time employed during time trials (SMD: -0.36; 95% CI: -0.77, 0.05). The RPE tended to be lower with CAF and CHO compared with CHO isolated ingestion during steady-state exercise (SMD: -0.43; 95% CI: -0.91, 0.05) with no differences between conditions in performance trials (SMD: -0.05, 95% CI: -0.39, 0.29). Although most of the studies showed higher values of blood glucose when CHO was co-ingested with CAF compared with PLA, only two studies observed higher values with CHO and CAF co-ingestion with respect to the isolated intake of CHO. One study observed greater fat oxidation and lower glycogen use when CAF was added to CHO. In terms of cortisol levels, one study showed an increase in cortisol levels when CAF was co-ingested with CHO compared with PLA. In summary, concurrent CHO and CAF intake may produce an additive ergogenic effect respect of the isolated ingestion of CHO. This additive effect was present when CHO was provided by a 6-9% of CHO solution (maltodextrin/dextrin + fructose) and CAF is administered in a dose of 4-6.5 mg/kg.

Interaction Between Caffeine and Creatine When Used as Concurrent Ergogenic Supplements: A Systematic Review.

There is some controversy regarding the interactions between creatine (CRE) and caffeine (CAF) supplements. The aim of this systematic review was to study whether such ergogenic interaction occurs and to analyze the protocol to optimize their synchronous use. The PubMed, Web of Science, MEDLINE, CINAHL, and SPORTDiscus databases were searched until November 2021 following the PRISMA guidelines. Ten studies were included. Three studies observed that CRE loading before an acute dose of CAF before exercise did not interfere in the beneficial effect of CAF, whereas one study reported that only an acute supplementation (SUP) of CAF was beneficial but not the acute SUP of both. When chronic SUP with CRE + CAF was used, two studies reported that CAF interfered in the beneficial effect of CRE, whereas three studies did not report interaction between concurrent SUP, and one study reported synergy. Possible mechanisms of interaction are opposite effects on relaxation time and gastrointestinal distress derived from concurrent SUP. CRE loading does not seem to interfere in the acute effect of CAF. However, chronic SUP of CAF during CRE loading could interfere in the beneficial effect of CRE.

Effects of Nitrate Supplementation on Muscle Strength and Mass: A Systematic Review.

ABSTRACT: Anderson, OK, Martinez-Ferran, M, Lorenzo-Calvo, J, Jiménez, SL, and Pareja-Galeano, H. Effects of nitrate supplementation on muscle strength and mass: a systematic review. J Strength Cond Res 36(12): 3562-3570, 2022-This systematic review examines the effect of dietary nitrate supplementation (SUP) on muscle strength and hypertrophy when combined with physical exercise. The databases PubMed, Web of Science, and MEDLINE were searched for full-text articles published between January 2000 and June 2020. For inclusion, studies had to report on the effects of SUP administered as acute or chronic doses together with a standardized exercise protocol on muscle strength and hypertrophy compared with placebo in healthy adults who were sedentary, physically active, or professional athletes. Twelve studies (1,571 subjects) were finally selected. In 5 studies, the SUP regime was acute, and in 7, it was chronic. SUP was nitrate-rich beetroot juice in 9 studies, a potassium nitrate capsule in 1, and increased dietary nitrate in 2. Ingested nitrate was 64-1,200 mg. Of the 12 studies, 6 observed an ergogenic effect of SUP compared with placebo. These findings indicate that muscle strength gains are possible provided the dose, format, frequency, period, and exercise test are appropriate. Best results were observed with a minimum acute dose of 400 mg of nitrate provided as beetroot juice/shot taken 2-2.5 hours before exercise involving low- and high-intensity muscle contractions. This SUP regime seems to improve muscle efficiency in terms of reduced phosphocreatine and energy costs (P-magnetic resonance spectroscopy) and improved time to exhaustion.

Genetic variations associated with non-contact muscle injuries in sport: A systematic review.

INTRODUCTION: Non-contact muscle injuries (NCMI) account for a large proportion of sport injuries, affecting athletes' performance and career, team results and financial aspects. Recently, genetic factors have been attributed a role in the susceptibility of an athlete to sustain NCMI. However, data in this field are only just starting to emerge. OBJECTIVES: To review available knowledge of genetic variations associated with sport-related NCMI. METHODS: The databases Pubmed, Scopus, and Web of Science were searched for relevant articles published until February 2021. The records selected for review were original articles published in peer-reviewed journals describing studies that have examined NCMI-related genetic variations in adult subjects (17-60 years) practicing any sport. The data extracted from the studies identified were as follows: general information, and data on genetic polymorphisms and NCMI risk, incidence and recovery time and/or severity. RESULTS: Seventeen studies examining 47 genes and 59 polymorphisms were finally included. 29 polymorphisms affecting 25 genes were found significantly associated with NCMI risk, incidence, recovery time, and/or severity. These genes pertain to three functional categories: (i) muscle fiber structural/contractile properties, (ii) muscle repair and regeneration, or (iii) muscle fiber external matrix composition and maintenance. CONCLUSION: Our review confirmed the important role of genetics in NCMI. Some gene variants have practical implications such as differences of several weeks in recovery time detected between genotypes. Knowledge in this field is still in its early stages. Future studies need to examine a wider diversity of sports and standardize their methods and outcome measures.

Non-coding RNAs and Coronary Artery Disease.

Coronary artery disease (CAD) is the leading death cause worldwide. Non-coding RNA (ncRNA) are key regulators of genetic expression and thus can affect directly or indirectly the development and progression of different diseases. ncRNA can be classified in several types depending on the length or structure, as long non-coding RNA (lncRNA), microRNA (miRNA) and circularRNA (circRNA), among others. These types of RNA are present within cells or in circulation, and for this reason they have been used as biomarkers of different diseases, therefore revolutionizing precision medicine. Recent research studied the capability of circulating ncRNA to inform about CAD presence and predict the outcome of the disease. In this chapter we present a list of the miRNA, lncRNA and circRNA which are potential biomarkers of CAD.

Physical exercise and Prader-Willi syndrome: A systematic review.

OBJECTIVE: The aim of this systematic review was to summarize evidence on the acute responses of individuals with Prader-Willi syndrome (PWS) to physical exercise, and on the effectiveness of long-term exercise interventions to improve the clinical manifestations of this syndrome. DESIGN/METHODS: Relevant articles were identified in the electronic databases PubMed, Medline, CINAHL and SPORTDiscus (from inception to December 2018). Twenty-two studies including a total of 356 patients with PWS met all inclusion criteria and were included in the review. RESULTS: Patients with PWS present with a decreased physical performance and impaired cardiorespiratory (maximal oxygen consumption, heart rate recovery after exercise) and hormonal (growth hormone release) responses to exercise. Most long-term exercise interventions have proven to decrease body mass while improving physical performance. Some benefits have also been reported in biochemical (glucose homeostasis, lipid profile) and biomechanical (gait pattern) variables, although there is controversy regarding the effects on body composition. No exercise-related adverse events have been reported in patients with PWS. CONCLUSION: Physical exercise seems to be safe and effective for improving several phenotypes in PWS, notably physical fitness. However, further research is needed to confirm these results and especially to corroborate whether exercise per se or combined with dietary intervention is an effective coadjuvant treatment for reducing body mass in these patients.

Supplements with purported effects on muscle mass and strength.

PURPOSE: Several supplements are purported to promote muscle hypertrophy and strength gains in healthy subjects, or to prevent muscle wasting in atrophying situations (e.g., ageing or disuse periods). However, their effectiveness remains unclear. METHODS: This review summarizes the available evidence on the beneficial impacts of several popular supplements on muscle mass or strength. RESULTS: Among the supplements tested, nitrate and caffeine returned sufficient evidence supporting their acute beneficial effects on muscle strength, whereas the long-term consumption of creatine, protein and polyunsaturated fatty acids seems to consistently increase or preserve muscle mass and strength (evidence level A). On the other hand, mixed or unclear evidence was found for several popular supplements including branched-chain amino acids, adenosine triphosphate, citrulline, ß-Hydroxy-ß-methylbutyrate, minerals, most vitamins, phosphatidic acid or arginine (evidence level B), weak or scarce evidence was found for conjugated linoleic acid, glutamine, resveratrol, tribulus terrestris or ursolic acid (evidence level C), and no evidence was found for other supplements such as ornithine or α-ketoglutarate (evidence D). Of note, although most supplements appear to be safe when consumed at typical doses, some adverse events have been reported for some of them (e.g., caffeine, vitamins, α-ketoglutarate, tribulus terrestris, arginine) after large intakes, and there is insufficient evidence to determine the safety of many frequently used supplements (e.g., ornithine, conjugated linoleic acid, ursolic acid). CONCLUSION:  In summary, despite their popularity, there is little evidence supporting the use of most supplements, and some of them have been even proven ineffective or potentially associated with adverse effects.

Physical Activity and Sedentary Behavior at the End of the Human Lifespan.

To objectively assess physical activity levels and sedentary behavior in a cohort of Spanish centenarians and their nonagenarian peers. Physical activity and sedentary behavior patterns were objectively measured by an ActiGraph GT3X accelerometer in centenarians (n = 18; 83% women; 100.8 ± 0.8 [100-103] years) and nonagenarians (n = 11; 91% women; 93.3 ± 2.5 [90-98] years). Centenarians showed less counts per minute (17.6 ± 7.1 vs. 46.1 ± 23.7, p = .003, d = 1.851) and steps per day (455 ± 237 vs. 1,249 ± 776, p = .007, d = 1.587) than nonagenarians. The daily number of sedentary breaks was also lower in the former (5.0 ± 1.5 vs. 6.7 ± 2.0, p = .019, d = 0.971). When observing time distribution, the most active day period in both groups was the morning, with a peak between 10:00 and 11:59. This data suggest that the decline in physical activity levels continues to worsen until the end of the human lifespan.

Comparison of the Abdominal Wall Muscle Thickness in Female Rugby Players Versus Non-Athletic Women: A Cross-Sectional Study.

Background and Objectives: Rugby players engage in demanding, high loading muscular activity in the spine. Study of the abdominal wall architecture in female rugby athletes is relevant to the possible muscular asymmetry secondary to sport practice and the relationship between the abdominal wall and the pelvic floor muscles. Activation of the transversus abdominis (TrAb) generates an increase in the bladder neck muscle. Moreover, an increased interrecti distance (IRD) is related to urinary incontinence and has a higher prevalence in athletic women. The aim of the present study was to compare and quantify, with ultrasound imaging (USI), the thickness of the transversus abdominis (TrAb), external oblique (EO), internal oblique (IO), rectus abdominis (RA), and interrecti distance (IRD) in female rugby players versus non-athletic women in order to improve upon existing knowledge about abdominal wall configuration in female athletes. Materials and Methods: A sample of 32 women was recruited at the Universidad Europea Research Lab and divided in two groups: a rugby group (n = 16) and a non-athletic women group (n = 16). The thickness of the TrAb, EO, IO, RA, and IRD were assessed by USI in both groups. Results: There were statistically significant differences for the ultrasound evaluation thickness of the right TrAb (p = 0.011; d = 0.10), EO (p = 0.045; d = 0.74), IO (p = 0.003; d = 1.32), and RA (p = 0.001; d = 1.38) showing a thickness increase for the rugby group with respect to the control group. For the IRD thickness, there were no significant differences (p > 0.05) between groups. Conclusions: An increased TrAb, IO, EO, and RA thickness may be shown in female rugby players versus non-athletic women. Nevertheless, statistically relevant differences were not found for the IRD between both groups.

Genotypic and phenotypic features of all Spanish patients with McArdle disease: a 2016 update.

BACKGROUND: We recently described the genotype/phenotype features of all Spanish patients diagnosed with McArdle disease as of January 2011 (n = 239, prevalence of ~1/167,000) (J Neurol Neurosurg Psychiatry 2012;83:322-8). Several caveats were however identified suggesting that the prevalence of the disease is actually higher. METHODS: We have now updated main genotype/phenotype data, as well as potential associations within/between them, of all Spanish individuals currently diagnosed with McArdle disease (December 2016). RESULTS: Ninety-four new patients (all Caucasian) have been diagnosed, yielding a prevalence of ~1/139,543 individuals. Around 55% of the mutated alleles have the commonest PYGM pathogenic mutation p.R50X, whereas p.W798R and p.G205S account for 10 and 9% of the allelic variants, respectively. Seven new mutations were identified: p.H35R, p.R70C, p.R94Q, p.L132WfsX163, p.Q176P, p.R576Q, and c.244-3_244-2CA. Almost all patients show exercise intolerance, the second wind phenomenon and high serum creatine kinase activity. There is, however, heterogeneity in clinical severity, with 8% of patients being asymptomatic during normal daily life, and 21% showing limitations during daily activities and fixed muscle weakness. A major remaining challenge is one of diagnosis, which is often delayed until the third decade of life in 72% of new patients despite the vast majority (86%) reporting symptoms before 20 years. An important development is the growing proportion of those reporting a 4-year improvement in disease severity (now 34%) and following an active lifestyle (50%). Physically active patients are more likely to report an improvement after a 4-year period in the clinical course of the disease than their inactive peers (odds ratio: 13.98; 95% confidence interval: 5.6, 34.9; p < 0.001). Peak oxygen uptake is also higher in the former (20.7 ± 6.0 vs. 16.8 ± 5.3 mL/kg/min, p = 0.0013). Finally, there is no association between PYGM genotype and phenotype manifestation of the disease. CONCLUSIONS: The reported prevalence of McArdle disease grows exponentially despite frequent, long delays in genetic diagnosis, suggesting that many patients remain undiagnosed. Until a genetic cure is available (which is not predicted in the near future), current epidemiologic data support that adoption of an active lifestyle is the best medicine for these patients.

'Adipaging': ageing and obesity share biological hallmarks related to a dysfunctional adipose tissue.

The increasing ageing of our societies is accompanied by a pandemic of obesity and related cardiometabolic disorders. Progressive dysfunction of the white adipose tissue is increasingly recognized as an important hallmark of the ageing process, which in turn contributes to metabolic alterations, multi-organ damage and a systemic pro-inflammatory state ('inflammageing'). On the other hand, obesity, the paradigm of adipose tissue dysfunction, shares numerous biological similarities with the normal ageing process such as chronic inflammation and multi-system alterations. Accordingly, understanding the interplay between accelerated ageing related to obesity and adipose tissue dysfunction is critical to gain insight into the ageing process in general as well as into the pathophysiology of obesity and other related conditions. Here we postulate the concept of 'adipaging' to illustrate the common links between ageing and obesity and the fact that, to a great extent, obese adults are prematurely aged individuals.

IPSCs, a Promising Tool to Restore Muscle Atrophy.

Induced pluripotent stem cells (iPSCs) are a promising tool for regenerative medicine in chronic conditions associated with muscle atrophy since iPSCs are easier to obtain, pose less ethical limitations and can better capture human genetic diversity compared with human embryonic stem cells. We highlight the potentiality of iPSCs for treating muscle-affecting conditions for which no effective cure is yet available, notably aging sarcopenia and inherited neurometabolic conditions. J. Cell. Physiol. 231: 259-260, 2016. © 2015 Wiley Periodicals, Inc.

Galectin-3, osteopontin and successful aging.

BACKGROUND: Individuals who reach exceptional longevity (100+ years of age) free of common chronic age diseases (i.e. 'dodgers') arguably represent the paradigm of successful aging in humans. As such, identification of potential biomarkers associated with this phenomenon is of medical interest. METHODS: We measured serum levels of galectin-3 and osteopontin, both of which have been shown to be linked with major chronic or aging-related disorders in younger populations, in centenarian 'dodgers' (n=81; 40 men; 100-104 years) and healthy controls (n=41; 24 men, 70-80 years). RESULTS: Both biomarkers showed significantly lower values (p<0.001) in the former (galectin-3: 2.4±1.7 vs. 4.8±2.8 ng/mL; osteopontin: 38.1±27.7 vs. 72.6±33.1 µg/mL). Logistic regression analysis identified the combination of these two biomarkers as a significant predictor variable associated with successful aging regardless of sex (p<0.001). The area under the curve (AUC) classified the ability of galectin-3 and osteopontin to predict the likelihood of successful aging as 'fair' (AUC=0.75) and 'good' (AUC=0.80), respectively. Particularly, the combination of the two biomarkers showed good discriminatory power for successful aging (AUC=0.86), with sensitivity=83% and specificity=74%. CONCLUSIONS: Lower levels of both galectin-3 and osteopontin are associated with successful aging, representing potential biomarkers of this condition. Our cross-sectional data must be however approached with caution. Further research is necessary to replicate the present preliminary results in other cohorts and to identify the potential use of galectin-3 and osteopontin as potential targets (or at least predictors) in future personalized anti-aging therapies.

Baicalin supplementation reduces serum biomarkers of skeletal muscle wasting and may protect against lean body mass reduction in cancer patients: Results from a pilot open-label study.

OBJECTIVES: Muscle wasting in patients with cancer has been linked to an increased activity of nuclear factor κB (NF-κB) and higher circulating levels of activin-A (ActA), a negative growth factor for muscle mass. Baicalin is a natural flavonoid that can reduce skeletal muscle atrophy in animal models of cancer cachexia by inhibiting NF-κB. This pilot open-label study assessed the effects of baicalin supplementation (50 mg daily for 3 months) in cancer patients who showed involuntary weight loss >5% over the past 6 months. METHODS: A total of 20 patients were investigated. Participants were evaluated at baseline and at the end of the 3-month study period for the following endpoints: 1) changes from baseline in serum NF-κB and ActA levels; and 2) change from baseline in lean body mass (LBM). RESULTS: We observed significant reduction in both NF-κB (p<0.05) and ActA (p<0.05) serum levels from baseline to 3 months. At 3 months, patients also showed a significant mean increase in LBM (+0.8 kg, p<0.05 compared with baseline). CONCLUSION: Our pilot open-label data suggest that baicalin supplementation is potentially useful for contrasting lean body mass reduction in cancer patients with involuntary weight loss, an effect which is likely mediated by the inhibition of negative growth factors for muscle mass.

Rationale and Design of a Randomized Controlled Trial Evaluating Whole Muscle Exercise Training Effects in Outpatients with Pulmonary Arterial Hypertension (WHOLEi+12).

BACKGROUND AND AIMS: Physical exercise is an important component in the management of pulmonary artery hypertension (PAH). The aim of this randomized controlled trial (RCT) is to determine the effects of an 8-week intervention combining muscle resistance, aerobic and inspiratory pressure load exercises in PAH outpatients. METHODS: The RCT will be conducted from September 2015 to September 2016 following the recommendations of the Consolidated Standards of Reported Trials (CONSORT), with a total sample size of n ≥ 48 (≥24 participants/group). We will determine the effects of the intervention on: (i) skeletal-muscle power and mass (primary end points); and (ii) NT-proBNP, cardiopulmonary exercise testing variables (VO2peak, ventilatory equivalent for CO2 at the anaerobic threshold (VE/VCO2 at the AT), end-tidal pressure of CO2 at the anaerobic threshold (PETCO2 at the AT), 6-min walking distance (6MWD), maximal inspiratory pressure (PImax), health-related quality of life (HRQoL), objectively-assessed spontaneous levels of physical activity, and safety (secondary end points). CONCLUSIONS AND PERSPECTIVES: This trial will provide insight into biological mechanisms of the disease and indicate the potential benefits of exercise in PAH outpatients, particularly on muscle power.

p16INK4a, NAD(+) , and sestrins: new targets for combating aging-related chronic illness?

Aging-related chronic illness is a price we have to pay to live longer. Prevalent among the oldest old, the condition limits their functional independence and also aggravates the course of several age-related chronic diseases. Thus, the search is on for efficient therapies that will mitigate age-related pathologies. In this article, we point out the potential clinical implications of recent provocative basic research in the field. New possible targets have been recently discovered, are clearly involved in age-related pathologies and might benefit the treatment of other age-related conditions, particularly metabolic diseases.