Molecular aging and rejuvenation of human muscle stem cells

Very little remains known about the regulation of human organ stem cells (in general, and during the aging process), and most previous data were collected in short-lived rodents. We examined whether stem cell aging in rodents could be extrapolated to genetically and environmentally variable humans. Our findings establish key evolutionarily conserved mechanisms of human stem cell aging. We find that satellite cells are maintained in aged human skeletal muscle, but fail to activate in response to muscle attrition, due to diminished activation of Notch compounded by elevated transforming growth factor beta (TGF-β)/phospho Smad3 (pSmad3). Furthermore, this work reveals that mitogen-activated protein kinase (MAPK)/phosphate extracellular signal-regulated kinase (pERK) signalling declines in human muscle with age, and is important for activating Notch in human muscle stem cells. This molecular understanding, combined with data that human satellite cells remain intrinsically young, introduced novel therapeutic targets. Indeed, activation of MAPK/Notch restored ‘youthful’ myogenic responses to satellite cells from 70-year-old humans, rendering them similar to cells from 20-year-old humans. These findings strongly suggest that aging of human muscle maintenance and repair can be reversed by ‘youthful’ calibration of specific molecular pathways

Relative sit-to-stand power: aging trajectories, functionally relevant cut-off points, and normative data in a large European cohort

Background: A validated, standardized, and feasible test to assess muscle power in older adults has recently been reported: the sit-to-stand (STS) muscle power test. This investigation aimed to assess the relationship between relative STS power and age and to provide normative data, cut-off points, and minimal clinically important differences (MCID) for STS power measures in older women and men. Methods: A total of 9320 older adults (6161 women and 3159 men) aged 60–103 years and 586 young and middle-aged adults (318 women and 268 men) aged 20–60 years were included in this cross-sectional study. Relative (normalized to body mass), allometric (normalized to height squared), and specific (normalized to legs muscle mass) muscle power values were assessed by the 30 s STS power test. Body composition was evaluated by dual energy X-ray absorptiometry and bioelectrical impedance analysis, and legs skeletal muscle index (SMI; normalized to height squared) was calculated. Habitual and maximal gait speed, timed up-and-go test, and 6 min walking distance were collected as physical performance measures, and participants were classified into two groups: well-functioning and mobility-limited older adults. Results: Relative STS power was found to decrease between 30–50 years (-0.05 W·kg-1·year-1; P > 0.05), 50–80 years (-0.10 to -0.13 W·kg-1·year-1; P < 0.001), and above 80 years (-0.07 to -0.08 W·kg-1·year-1; P < 0.001). A total of 1129 older women (18%) and 510 older men (16%) presented mobility limitations. Mobility-limited older adults were older and exhibited lower relative, allometric, and specific power; higher body mass index (BMI) and legs SMI (both only in women); and lower legs SMI (only in men) than their well-functioning counterparts (all P < 0.05). Normative data and cut-off points for relative, allometric, and specific STS power and for BMI and legs SMI were reported. Low relative STS power occurred below 2.1 W·kg-1 in women (area under the curve, AUC, [95% confidence interval, CI] = 0.85 [0.84–0.87]) and below 2.6 W·kg-1 in men (AUC [95% CI] = 0.89 [0.87–0.91]). The age-adjusted odds ratios [95% CI] for mobility limitations in older women and men with low relative STS power were 10.6 [9.0–12.6] and 14.1 [10.9–18.2], respectively. MCID values for relative STS power were 0.33 W·kg-1 in women and 0.42 W·kg-1 in men. Conclusions: Relative STS power decreased significantly after the age of 50 years and was negatively and strongly associated with mobility limitations. Our study provides normative data, functionally relevant cut-off points, and MCID values for STS power for their use in daily clinical practice. © 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders

On-ground performance tests of the SAX/PDS detector

The Phoswich Detection System (PDS) is one of the four narrow field experiments on board the SAX satellite. The PDS will be dedicated to deep temporal and spectral studies of celestial X-ray sources in the 15–300 keV energy band. It also includes a gamma-ray burst monitor. The PDS detector is composed of 4 actively shielded NaI(Tl)/CsI(Na) phoswich scintillators with a total geometric area of 795 cm2 and a field of view of 1:4 (FWHM). The performance of the detector, before its integration with its flight electronic, was tested using standard instrumentation. Here we present results of these tests. The measured energy resolution of the phoswich units is better than 15% at 60 keV, confirming the expectations. Also test results of the anticoincidence shield of CsI(Na) and collimator are discussed

Effectiveness of physiotherapy exercise following hip arthroplasty for osteoarthritis: a systematic review of clinical trials

Background: Physiotherapy has long been a routine component of patient rehabilitation following hip joint replacement. The purpose of this systematic review was to evaluate the effectiveness of physiotherapy exercise after discharge from hospital on function, walking, range of motion, quality of life and muscle strength, for osteoarthritic patients following elective primary total hip arthroplasty. Methods: Design: Systematic review, using the Cochrane Collaboration Handbook for Systematic Reviews of Interventions and the Quorom Statement. Database searches: AMED, CINAHL, EMBASE, KingsFund, MEDLINE, Cochrane library (Cochrane reviews, Cochrane Central Register of Controlled Trials, DARE), PEDro, The Department of Health National Research Register. Handsearches: Physiotherapy, Physical Therapy, Journal of Bone and Joint Surgery (Britain) Conference Proceedings. No language restrictions were applied. Selection: Trials comparing physiotherapy exercise versus usual/standard care, or comparing two types of relevant exercise physiotherapy, following discharge from hospital after elective primary total hip replacement for osteoarthritis were reviewed. Outcomes: Functional activities of daily living, walking, quality of life, muscle strength and range of hip joint motion. Trial quality was extensively evaluated. Narrative synthesis plus meta-analytic summaries were performed to summarise the data. Results: 8 trials were identified. Trial quality was mixed. Generally poor trial quality, quantity and diversity prevented explanatory meta-analyses. The results were synthesised and meta-analytic summaries were used where possible to provide a formal summary of results. Results indicate that physiotherapy exercise after discharge following total hip replacement has the potential to benefit patients. Conclusion: Insufficient evidence exists to establish the effectiveness of physiotherapy exercise following primary hip replacement for osteoarthritis. Further well designed trials are required to determine the value of post discharge exercise following this increasingly common surgical procedure

Muscle strength, gait, and balance in 20 patients with hip osteoarthritis followed for 2 years after THA

Background Patients with hip osteoarthritis (OA) have muscular weakness, impaired balance, and limp. Deficits in the different limb muscles and their recovery courses are largely unknown, however. We hypothesized that there is persisting muscular weakness in lower limb muscles and an impaired balance and gait 2 years after THA

An appraisal of rehabilitation regimes used for improving functional outcome after total hip replacement surgery

This study aimed to systematically review the literature with regards to studies of rehabilitation programmes that have tried to improve function after total hip replacement (THR) surgery. 15 randomised controlled trials were identified of which 11 were centre-based, 2 were home based and 2 were trials comparing home and centre based interventions. The use of a progressive resistance training (PRT) programme led to significant improvement in muscle strength and function if the intervention was carried out early (< 1 month following surgery) in a centre (6/11 centre-based studies used PRT), or late (> 1 month following surgery) in a home based setting (2/2 home based studies used PRT). In direct comparison, there was no difference in functional measures between home and centre based programmes (2 studies), with PRT not included in the regimes prescribed. A limitation of the majority of these intervention studies was the short period of follow up. Centre based program delivery is expensive as high costs are associated with supervision, facility provision, and transport of patients. Early interventions are important to counteract the deficit in muscle strength in the affected limb, as well as persistent atrophy that exists around the affected hip at 2 years post-operatively. Studies of early home-based regimes featuring PRT with long term follow up are needed to address the problems currently associated with rehabilitation following THR

Changes in muscle contractile characteristics and jump height following 24 days of unilateral lower limb suspension

We measured changes in maximal voluntary and electrically evoked torque and rate of torque development because of limb unloading. We investigated whether these changes during single joint isometric muscle contractions were related to changes in jump performance involving dynamic muscle contractions and several joints. Six healthy male subjects (21 ± 1 years) underwent 3 weeks of unilateral lower limb suspension (ULLS) of the right limb. Plantar flexor and knee extensor maximal voluntary contraction (MVC) torque and maximal rate of torque development (MRTD), voluntary activation, and maximal triplet torque (thigh; 3 pulses at 300 Hz) were measured next to squat jump height before and after ULLS. MVC of plantar flexors and knee extensors (MVCke) and triplet torque decreased by 12% (P = 0.012), 21% (P = 0.001) and 11% (P = 0.016), respectively. Voluntary activation did not change (P = 0.192). Absolute MRTD during voluntary contractions decreased for plantar flexors (by 17%, P = 0.027) but not for knee extensors (P = 0.154). Absolute triplet MRTD decreased by 17% (P = 0.048). The reduction in MRTD disappeared following normalization to MVC. Jump height with the previously unloaded leg decreased significantly by 28%. No significant relationships were found between any muscle variable and jump height (r < 0.48), but decreases in torque were (triplet, r = 0.83, P = 0.04) or tended to be (MVCke r = 0.71, P = 0.11) related to decreases in jump height. Thus, reductions in isometric muscle torque following 3 weeks of limb unloading were significantly related to decreases in the more complex jump task, although torque in itself (without intervention) was not related to jump performance

Dutch guideline on total hip prosthesis

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