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Abstract Background Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for anabolic reactions. We hypothesize that a similar metabolic remodelling occurs during skeletal muscle hypertrophy. Methods We used mass spectrometry in hypertrophying C2C12 myotubes in vitro and plantaris mouse muscle in vivo and assessed metabolomic changes and the incorporation of the [U‐13C6]glucose tracer. We performed enzyme inhibition of the key serine synthesis pathway enzyme phosphoglycerate dehydrogenase (Phgdh) for further mechanistic analysis and conducted a systematic review to align any changes in metabolomics during muscle growth with published findings. Finally, the UK Biobank was used to link the findings to population level. Results The metabolomics analysis in myotubes revealed insulin‐like growth factor‐1 (IGF‐1)‐induced altered metabolite concentrations in anabolic pathways such as pentose phosphate (ribose‐5‐phosphate/ribulose‐5‐phosphate: +40%; P = 0.01) and serine synthesis pathway (serine: −36.8%; P = 0.009). Like the hypertrophy stimulation with IGF‐1 in myotubes in vitro, the concentration of the dipeptide l‐carnosine was decreased by 26.6% (P = 0.001) during skeletal muscle growth in vivo. However, phosphorylated sugar (glucose‐6‐phosphate, fructose‐6‐phosphate or glucose‐1‐phosphate) decreased by 32.2% (P = 0.004) in the overloaded muscle in vivo while increasing in the IGF‐1‐stimulated myotubes in vitro. The systematic review revealed that 10 metabolites linked to muscle hypertrophy were directly associated with glycolysis and its interconnected anabolic pathways. We demonstrated that labelled carbon from [U‐13C6]glucose is increasingly incorporated by ~13% (P = 0.001) into the non‐essential amino acids in hypertrophying myotubes, which is accompanied by an increased depletion of media serine (P = 0.006). The inhibition of Phgdh suppressed muscle protein synthesis in growing myotubes by 58.1% (P

Abstract Datasets consist of measurement data and metadata. Metadata provides context, essential for understanding and (re-)using data. Various metadata standards exist for different methods, systems and contexts. However, relevant information resides at differing stages across the data-lifecycle. Often, this information is defined and standardized only at publication stage, which can lead to data loss and workload increase. In this study, we developed Metadatasheet, a metadata standard based on interviews with members of two biomedical consortia and systematic screening of data repositories. It aligns with the data-lifecycle allowing synchronous metadata recording within Microsoft Excel, a widespread data recording software. Additionally, we provide an implementation, the Metadata Workbook, that offers user-friendly features like automation, dynamic adaption, metadata integrity checks, and export options for various metadata standards. By design and due to its extensive documentation, the proposed metadata standard simplifies recording and structuring of metadata for biomedical scientists, promoting practicality and convenience in data management. This framework can accelerate scientific progress by enhancing collaboration and knowledge transfer throughout the intermediate steps of data creation.

Abstract Background A typical training plan is a mix of many training sessions with different intensities and durations to achieve a specific goal, like running a marathon in a certain time. Scientific publications provide little specific information to aid in writing a comprehensive training plan. This review aims to systematically and quantitatively analyse the last 12 weeks before a marathon as recommended in 92 sub-elite training plans. Methods We retrieved 92 marathon training plans and linked their running training sessions to five intensity zones. Subsequently, each training plan was grouped based on the total running volume in peak week into high (> 90 km/week), middle (65–90 km/week), and low (

Abstract Airborne transmission of pathogens plays a major role in the spread of infectious diseases. Aerosol particle production from the lung is thought to occur in the peripheral airways. In the present study we investigated eighty lung-healthy subjects of two age groups (20–39, 60–76 years) at rest and during exercise whether lung function parameters indicative of peripheral airway function were correlated with individual differences in aerosol particle emission. Lung function comprised spirometry and impulse oscillometry during quiet breathing and an expiratory vital capacity manoeuvre, using resistance (R5) and reactance at 5 Hz (X5) as indicators potentially related to peripheral airway function. The association between emission at different ventilation rates relative to maximum ventilation and lung function was assessed by regression analysis. In multiple regression analyses including age group, only vital capacity manoeuvre R5 at 15% to 50% of end-expiratory vital capacity as well as quiet breathing X5 were independently linked to particle emission at 20% to 50% of maximum ventilation, in addition to age group. The fact that age as predictive factor was still significant, although to a lower degree, points towards further effects of age, potentially involving surface properties not accounted for by impulse oscillometry parameters.

Abstract The maximal lactate steady state, abbreviated as MLSS, is the maximal exercise intensity where the concentration of earlobe capillary or arterial blood lactate remains constant over time. In the late 1970s and early 1980s, we (i.e. Hermann Heck and co-workers) developed a direct test to determine the MLSS to investigate whether it occurred at a lactate concentration of 4 mmol.L− 1, as earlier predicted by Alois Mader and colleagues. The test consisted of each participant performing several constant-intensity running bouts of ≈ 30 min at intensities close to the estimated MLSS. During each run, we measured lactate every 5 min. Based on the results, we defined the MLSS as the “workload where the concentration of blood lactate does not increase more than 1 mmo.L − 1 during the last 20 min of a constant load exercise”. This MLSS protocol is impractical for performance testing as it requires too many exercise bouts, but it is a gold standard to determine the real MLSS. It is especially useful to validate indirect tests that seek to estimate the MLSS.

Abstract Background Patients with critical illness can lose more than 15% of muscle mass in one week, and this can have long-term detrimental effects. However, there is currently no synthesis of the data of intensive care unit (ICU) muscle wasting studies, so the true mean rate of muscle loss across all studies is unknown. The aim of this project was therefore to systematically synthetise data on the rate of muscle loss and to identify the methods used to measure muscle size and to synthetise data on the prevalence of ICU-acquired weakness in critically ill patients. Methods We conducted a systematic literature search of MEDLINE, PubMed, AMED, BNI, CINAHL, and EMCARE until January 2022 (International Prospective Register of Systematic Reviews [PROSPERO] registration: CRD420222989540. We included studies with at least 20 adult critically ill patients where the investigators measured a muscle mass-related variable at two time points during the ICU stay. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and assessed the study quality using the Newcastle–Ottawa Scale. Results Fifty-two studies that included 3251 patients fulfilled the selection criteria. These studies investigated the rate of muscle wasting in 1773 (55%) patients and assessed ICU-acquired muscle weakness in 1478 (45%) patients. The methods used to assess muscle mass were ultrasound in 85% (n = 28/33) of the studies and computed tomography in the rest 15% (n = 5/33). During the first week of critical illness, patients lost every day −1.75% (95% CI −2.05, −1.45) of their rectus femoris thickness or −2.10% (95% CI −3.17, −1.02) of rectus femoris cross-sectional area. The overall prevalence of ICU-acquired weakness was 48% (95% CI 39%, 56%). Conclusion On average, critically ill patients lose nearly 2% of skeletal muscle per day during the first week of ICU admission.

Introduction: The measurement of physical frailty in elderly patients with orthopedic impairments remains a challenge due to its subjectivity, unreliability, time-consuming nature, and limited applicability to uninjured individuals. Our study aims to address this gap by developing objective, multifactorial machine models that do not rely on mobility data and subsequently validating their predictive capacity concerning the Timed-up-and-Go test (TUG test) in orthogeriatric patients. Methods: We utilized 67 multifactorial non-mobility parameters in a pre-processing phase, employing six feature selection algorithms. Subsequently, these parameters were used to train four distinct machine learning algorithms, including a generalized linear model, a support vector machine, a random forest algorithm, and an extreme gradient boost algorithm. The primary goal was to predict the time required for the TUG test without relying on mobility data. Results: The random forest algorithm yielded the most accurate estimations of the TUG test time. The best-performing algorithm demonstrated a mean absolute error of 2.7 s, while the worst-performing algorithm exhibited an error of 7.8 s. The methodology used for variable selection appeared to exert minimal influence on the overall performance. It is essential to highlight that all the employed algorithms tended to overestimate the time for quick patients and underestimate it for slower patients. Conclusion: Our findings demonstrate the feasibility of predicting the TUG test time using a machine learning model that does not depend on mobility data. This establishes a basis for identifying patients at risk automatically and objectively assessing the physical capacity of currently immobilized patients. Such advancements could significantly contribute to enhancing patient care and treatment planning in orthogeriatric settings.

Abstract Background Face masks are an effective, non-pharmacological strategy to reduce the transmission of Severe Acute Respiratory Syndrome Coronavirus-2 and other pathogens. However, it is a challenge to keep masks sealed during exercise, as ventilation can increase from 5 to 10 L/min at rest to up to 200 L/min so that masks may be blown away from the face. To reduce leakage e.g. during exercise, a face mask was developed that is taped onto the face. The aim of this study was to investigate during a graded exercise test the effect of a taped filter mask on the perception of breathlessness, heart rate, blood lactate concentration, and oxygen saturation when compared to a surgical mask and no mask. Methods Eight healthy trained participants (4 females), aged 24.5 ± 3.3 years performed graded exercise test until volitional exhaustion under three conditions: (1) No mask/control, (2) surgical mask or (3) taped filter mask. During these tests, we measured perception of breathlessness, heart rate, blood lactate concentration and peripheral oxygen saturation and analysed the resultant data with one or two-way repeated measures ANOVAs. We also used a questionnaire to evaluate mask comfort and analysed the data with paired t-tests. Results When compared to wearing no mask, maximal workload was significantly reduced with a taped filter face mask by 12 ± 6% (p 0.05). Moreover, subjects perceive the sensation of "severe breathlessness" at a 12 ± 9% lower workload (p = 0.012) with a taped face mask, and 7 ± 13% lower workload with a surgical mask (p > 0.05) when compared to wearing no mask. Oxygen saturation at 65% of the maximal workload is 1.5% lower (p = 0.018) with a taped mask than no mask. Heart rate and blood lactate concentration are not significantly different in-between no mask, surgical mask and taped mask at any workload. When compared to wearing a surgical mask, wearing a taped filter face mask has a significantly better wearing comfort (p = 0.038), feels better on the skin (p = 0.004), there is a lower sensation of moisture (p = 0.026) and wearers perceive that less heat is generated (p = 0.021). We found no sex/gender differences for any of the measured parameters. Conclusions A taped mask is well tolerated during light and moderate exercise intensity but reduces maximal exercise capacity.

Time is considered a primary barrier to exercise adherence. Therefore, developing time-efficient resistance training (RT) strategies that optimize muscular adaptations is of primary interest to practitioners. A novel approach to the problem involves combining intensive stretch protocols with RT. Conceivably, integrating stretch into the inter-set period may provide an added stimulus for muscle growth without increasing session duration. Mechanistically, stretch can regulate anabolic signaling via both active and passive force sensors. Emerging evidence indicates that both lengthening contractions against a high load as well as passive stretch can acutely activate anabolic intracellular signaling pathways involved in muscle hypertrophy. Although longitudinal research investigating the effects of stretching between RT sets is limited, some evidence suggests it may in fact enhance hypertrophic adaptations. Accordingly, the purpose of this paper is threefold: (1) to review how the active force of a muscle contraction and the force of a passive stretched are sensed; (2) to present evidence for the effectiveness of RT with inter-set stretch for muscle hypertrophy (3) to provide practical recommendations for application of inter-set stretch in program design as well as directions for future research.

Today, researchers, practitioners, and physicians measure the concentration of lactate during a graded exercise test to determine thresholds related to the maximal lactate steady state (maxLass) as a sensitive measure of endurance capacity. In the 1970s and 1980s, a group of Cologne-based researchers around Wildor Hollmann, Alois Mader, and Hermann Heck developed the methodology for systematic lactate testing and introduced a 4 mmol.L−1 lactate threshold. Later, they also developed the concept of the maxLass, and Mader designed a sophisticated mathematical model of human energy metabolism during exercise. Mader`s model simulates metabolic responses to exercise based on individual variables such as maximum oxygen uptake (V˙O2max) and the maximal rate of lactate formation (νLa.max). Mader’s model predicts that the νLa.max reduces the power at the anaerobic threshold and endurance performance but that a high νLa.max is required for events with high power outputs in elite athletes. Mader’s model also assumed before the millennium that the rate of fat oxidation is explained by the difference between glycolytic pyruvate synthesis and the actual rate of pyruvate oxidation which is consistent with current opinion. Mader’s model also simulated the V˙O2max slow component in the mid-1980s. Unfortunately, several landmark studies by the Cologne group were only published in German, and as a result, contributions by the Cologne group are under-appreciated in the English-speaking world. This narrative review aims to introduce key contributions of the Cologne group to human metabolism research especially for readers who do not speak German.

The aim of this study was to determine alterations of the metabolome in blood plasma in response to concentric-eccentric leg exercise performed at a simulated altitude of 3,500 m. To do so, we recruited 11 well-trained subjects and performed an untargeted metabolomics analysis of plasma samples obtained before, 20 min after as well as on day 8 after five sets of maximal, concentric-eccentric leg exercises that lasted 90 s each. We identified and annotated 115 metabolites through untargeted liquid chromatography-mass spectrometry metabolomics and used them to further calculate 20 sum/ratio of metabolites. A principal component analysis (PCA) revealed differences in-between the overall metabolome at rest and immediately after exercise. Interestingly, some systematic changes of relative metabolite concentrations still persisted on day 8 after exercise. The first two components of the PCA explained 34% of the relative concentrations of all identified metabolites analyzed together. A volcano plot indicates that 35 metabolites and two metabolite ratios were significantly changed directly after exercise, such as metabolites related to carbohydrate and TCA metabolism. Moreover, we observed alterations in the relative concentrations of amino acids (e.g., decreases of valine, leucine and increases in alanine) and purines (e.g., increases in hypoxanthine, xanthine and uric acid). In summary, high intensity concentric-eccentric exercise performed at simulated altitude systematically changed the blood metabolome in trained athletes directly after exercise and some relative metabolite concentrations were still changed on day 8. The importance of that persisting metabolic alterations on exercise performance should be studied further.

In skeletal muscle tissue, oxygen (O2) plays a pivotal role in both metabolism and the regulation of several intercellular pathways, which can modify proliferation, differentiation and survival of cells within the myogenic lineage. The concentration of oxygen in muscle tissue is reduced during embryogenesis and pathological conditions. Myogenic progenitor cells, namely satellite cells, are necessary for muscular regeneration in adults and are localized in a hypoxic microenvironment under the basal lamina, suggesting that the O2 level could affect their function. This review presents the effects of reduced oxygen levels (hypoxia) on satellite cell survival, myoblast regeneration and differentiation in vertebrates. Further investigations and understanding of the pathways involved in adult muscle regeneration during hypoxic conditions are maybe clinically relevant to seek for novel drug treatments for patients with severe muscle damage. We especially outlined the effect of hypoxia-inducible factor 1-alpha (HIF1A), the most studied transcriptional regulator of cellular and developmental response to hypoxia, whose investigation has recently been awarded with the Nobel price.

Resistance training promotes metabolic health and stimulates muscle hypertrophy, but the precise routes by which resistance exercise (RE) conveys these health benefits are largely unknown. Aim: To investigate how acute RE affects human skeletal muscle metabolism. Methods: We collected vastus lateralis biopsies from six healthy male untrained volunteers at rest, before the first of 13 RE training sessions, and 45 min after the first and last bouts of RE. Biopsies were analysed using untargeted mass spectrometry-based metabolomics. Results: We measured 617 metabolites covering a broad range of metabolic pathways. In the untrained state RE altered 33 metabolites, including increased 3-methylhistidine and N-lactoylvaline, suggesting increased protein breakdown, as well as metabolites linked to ATP (xanthosine) and NAD (N1-methyl-2-pyridone-5-carboxamide) metabolism; the bile acid chenodeoxycholate also increased in response to RE in muscle opposing previous findings in blood. Resistance training led to muscle hypertrophy, with slow type I and fast/intermediate type II muscle fibre diameter increasing by 10.7% and 10.4%, respectively. Comparison of post-exercise metabolite levels between trained and untrained state revealed alterations of 46 metabolites, including decreased N-acetylated ketogenic amino acids and increased beta-citrylglutamate which might support growth. Only five of the metabolites that changed after acute exercise in the untrained state were altered after chronic training, indicating that training induces multiple metabolic changes not directly related to the acute exercise response. Conclusion: The human skeletal muscle metabolome is sensitive towards acute RE in the trained and untrained states and reflects a broad range of adaptive processes in response to repeated stimulation.

Injuries, high altitude, and endurance exercise lead to hypoxic conditions in skeletal muscle and sometimes to hypoxia-induced local tissue damage. Thus, regenerative myoblasts/satellite cells are exposed to different levels and durations of partial oxygen pressure depending on the spatial distance from the blood vessels. To date, it is unclear how hypoxia affects myoblasts proliferation, differentiation, and particularly fusion with normoxic myoblasts. To study this, we investigated how 21% and 2% oxygen affects C2C12 myoblast morphology, proliferation, and myogenic differentiation and evaluated the fusion of normoxic- or hypoxic-preconditioned C2C12 cells in 21% or 2% oxygen in vitro. Out data show that the long-term hypoxic culture condition does not affect the proliferation of C2C12 cells but leads to rounder cells and reduced myotube formation when compared with myoblasts exposed to normoxia. However, when normoxic- and hypoxic-preconditioned myoblasts were differentiated together, the resultant myotubes were significantly larger than the control myotubes. Whole transcriptome sequencing analysis revealed several novel candidate genes that are differentially regulated during the differentiation under normoxia and hypoxia in mixed culture conditions and may thus be involved in the increase in myotube size. Taken together, oxygen-dependent adaption and interaction of myoblasts may represent a novel approach for the development of innovative therapeutic targets.

Exercise is recommended for the healthy population as it increases fitness and prevents diseases. Moreover, exercise is also applied as an adjunct therapy for patients with various chronic diseases including cancer. Childhood cancer is a rare, heterogeneous disease that differs from adult cancer. Improved therapeutic strategies have increased childhood cancer survival rates to above 80% in developed countries. Although this is higher than the average adult cancer survival rate of about 50%, therapy results often in substantial long-term side effects in childhood cancer survivors. Exercise in adult cancer patients has many beneficial effects and may slow down tumor progression and improve survival in some cancer types, suggesting that exercise may influence cancer cell behavior. In contrast to adults, there is not much data on general effects of exercise in children. Whilst it seems possible that exercise might delay cancer progression or improve survival in children as well, there is no reliable data yet to support this hypothesis. Depending on the type of cancer, animal studies of adult cancer types show that the exercise-induced increase of the catecholamines epinephrine and norepinephrine, have suppressive as well as promoting effects on cancer cells. The diverse effects of exercise in adult cancer patients require investigating whether these results can be achieved in children with cancer.

Endurance is not only a key factor in many sports but endurance-related variables are also associated with good health and low mortality. Twin and family studies suggest that several endurance-associated traits are ≈50% inherited. However, we still poorly understand what DNA sequence variants contribute to endurance heritability. To address this issue, we conducted a systematic review to identify genes whose experimental loss or gain-of-function increases endurance capacity in mice. We found 31 genes including two isoforms of Ppargc1a whose manipulation increases running or swimming endurance performance by up to 1800%. Genes whose gain-of-function increases endurance are Adcy5, Adcy8, Hk2, Il15, Mef2c, Nr4a3, Pck1 (Pepck), Ppard, Ppargc1a (both the a and b isoforms of the protein Pgc-1α), Ppargc1b, Ppp3ca (calcineurin), Scd1, Slc5a7, Tfe3, Tfeb, Trib3 & Trpv1. Genes whose loss-of-function increases endurance in mice are Actn3, Adrb2, Bdkrb2, Cd47, Crym, Hif1a, Myoz1, Pappa, Pknox1, Pten, Sirt4, Thbs1, Thra, and Tnfsf12. Of these genes, human DNA sequence variants of ACTN3, ADCY5, ADRB2, BDKRB2, HIF1A, PPARD, PPARGC1A, PPARGC1B, and PPP3CA are also associated with endurance capacity and/or VO2max trainability suggesting evolutionary conservation between mice and humans. Bioinformatical analyses show that there are numerous amino acid or copy number-changing DNA variants of endurance genes in humans, suggesting that genetic variation of endurance genes contributes to the variation of human endurance capacity, too. Moreover, several of these genes/proteins change their expression or phosphorylation in skeletal muscle or the heart after endurance exercise, suggesting a role in the adaptation to endurance exercise.

Skeletal muscle mass differs greatly in mice and humans and this is partially inherited. To identify muscle hypertrophy candidate genes we conducted a systematic review to identify genes whose experimental loss or gain-of-function results in significant skeletal muscle hypertrophy in mice. We found 47 genes that meet our search criteria and cause muscle hypertrophy after gene manipulation. They are from high to small effect size: Ski, Fst, Acvr2b, Akt1, Mstn, Klf10, Rheb, Igf1, Pappa, Ppard, Ikbkb, Fstl3, Atgr1a, Ucn3, Mcu, Junb, Ncor1, Gprasp1, Grb10, Mmp9, Dgkz, Ppargc1a (specifically the Ppargc1a4 isoform), Smad4, Ltbp4, Bmpr1a, Crtc2, Xiap, Dgat1, Thra, Adrb2, Asb15, Cast, Eif2b5, Bdkrb2, Tpt1, Nr3c1, Nr4a1, Gnas, Pld1, Crym, Camkk1, Yap1, Inhba, Tp53inp2, Inhbb, Nol3, Esr1. Knock out, knock down, overexpression or a higher activity of these genes causes overall muscle hypertrophy as measured by an increased muscle weight or cross sectional area. The mean effect sizes range from 5 to 345% depending on the manipulated gene as well as the muscle size variable and muscle investigated. Bioinformatical analyses reveal that Asb15, Klf10, Tpt1 are most highly expressed hypertrophy genes in human skeletal muscle when compared to other tissues. Many of the muscle hypertrophy-regulating genes are involved in transcription and ubiquitination. Especially genes belonging to three signaling pathways are able to induce hypertrophy: (a) Igf1-Akt-mTOR pathway, (b) myostatin-Smad signaling, and (c) the angiotensin-bradykinin signaling pathway. The expression of several muscle hypertrophy-inducing genes and the phosphorylation of their protein products changes after human resistance and high intensity exercise, in maximally stimulated mouse muscle or in overloaded mouse plantaris.

The aim of this study was to investigate the function of the Hippo pathway member Yes-associated protein (Yap, gene name Yap1) in skeletal muscle fibres in vivo. Specifically we bred an inducible, skeletal muscle fibre-specific knock-in mouse model (MCK-tTA-hYAP1 S127A) to test whether the over expression of constitutively active Yap (hYAP1 S127A) is sufficient to drive muscle hypertrophy or stimulate changes in fibre type composition. Unexpectedly, after 5-7 weeks of constitutive hYAP1 S127A over expression, mice suddenly and rapidly lost 20-25% body weight and suffered from gait impairments and kyphosis. Skeletal muscles atrophied by 34-40% and the muscle fibre cross sectional area decreased by ≈40% when compared to control mice. Histological analysis revealed evidence of skeletal muscle degeneration and regeneration, necrotic fibres and a NADH-TR staining resembling centronuclear myopathy. In agreement with the histology, mRNA expression of markers of regenerative myogenesis (embryonic myosin heavy chain, Myf5, myogenin, Pax7) and muscle protein degradation (atrogin-1, MuRF1) were significantly elevated in muscles from transgenic mice versus control. No significant changes in fibre type composition were detected using ATPase staining. The phenotype was largely reversible, as a cessation of hYAP1 S127A expression rescued body and muscle weight, restored muscle morphology and prevented further pathological progression. To conclude, high Yap activity in muscle fibres does not induce fibre hypertrophy nor fibre type changes but instead results in a reversible atrophy and deterioration.

BACKGROUND:Sarcopenia, the loss of muscle mass and function with age, is associated with increased morbidity and mortality. Current understanding of the underlying mechanisms is limited. Glucocorticoids (GC) in excess cause muscle weakness and atrophy. We hypothesized that GC may contribute to sarcopenia through elevated circulating levels or increased glucocorticoid receptor (GR) signaling by increased expression of either GR or the GC-amplifying enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11βHSD1) in muscle. METHODS:There were 82 participants; group 1 comprised 33 older men (mean age 70.2 years, SD 4.4) and 19 younger men (22.2 years, 1.7) and group 2 comprised 16 older men (79.1 years, 3.4) and 14 older women (80.1 years, 3.7). We measured muscle strength, mid-thigh cross-sectional area, fasting morning plasma cortisol, quadriceps muscle GR and 11βHSD1 mRNA, and urinary glucocorticoid metabolites. Data were analysed using multiple linear regression adjusting for age, gender and body size. RESULTS:Muscle strength and size were not associated with plasma cortisol, total urinary glucocorticoids or the ratio of urinary 5β-tetrahydrocortisol +5α-tetrahydrocortisol to tetrahydrocortisone (an index of systemic 11βHSD activity). Muscle strength was associated with 11βHSD1 mRNA levels (β -0.35, p = 0.04), but GR mRNA levels were not significantly associated with muscle strength or size. CONCLUSION:Although circulating levels of GC are not associated with muscle strength or size in either gender, increased cortisol generation within muscle by 11βHSD1 may contribute to loss of muscle strength with age, a key component of sarcopenia. Inhibition of 11βHSD1 may have therapeutic potential in sarcopenia.