ABSTRACT Background Oestrogen deficiency after menopause is associated with metabolic dysfunction and increased cardiovascular risk, which may contribute to declines in skeletal muscle health and the development of postmenopausal sarcopenia. Mitochondria are central to energy metabolism and cellular adaptation and have indicated that oestrogen modulates mitochondrial biogenesis, oxidative phosphorylation and redox balance. Exercise training is considered a promising non‐pharmacological intervention to counteract these adverse effects by improving mitochondrial and metabolic health. However, studies directly evaluating mitochondrial adaptations to exercise under oestrogen‐deficient conditions remain limited, and existing findings are inconsistent across experimental models. Methods Female Sprague–Dawley rats were randomly assigned to four groups: sham‐operated (S, n = 6), ovariectomy (O, n = 6), sham plus exercise (SE, n = 8) and ovariectomy plus exercise (OE, n = 8). Exercise training consisted of treadmill running (28 m/min, 60 min/day, 5 days/week) for 12 weeks. Body weight, uterine mass, metabolic parameters, aerobic capacity, mitochondrial‐related proteins and cardiac fibrosis were measured and analysed. Results Ovariectomy resulted in significant body weight gain ( p < 0.001) and uterine atrophy ( p < 0.001) compared with sham controls. After exercise training, peak V̇O 2 was significantly higher in exercise groups ( p < 0.001), indicating improved aerobic capacity under oestrogen‐deficient conditions. Serum glucose levels were markedly increased in OVX rats ( p < 0.001) and were partially normalized by exercise training ( p < 0.05). Serum growth differentiation factor 15 (GDF‐15) levels were elevated in the O group ( p < 0.01). Several mitochondrial electron transport chain (ETC) complexes were significantly upregulated in the SE group compared with the S and O groups ( p < 0.01), and Complex III expression was significantly higher in the OE group than in the O group ( p < 0.01). Complex IV showed only partial recovery in the OE group ( p < 0.05), and Complex V remained unchanged. Expression of pyruvate metabolism–related proteins was significantly lower in the O group ( p < 0.01), although both exercise groups showed higher expression levels than the O group ( p < 0.05). The expression of the mitochondrial biogenesis marker peroxisome proliferator–activated receptor‐γ coactivator‐1α (PGC‐1α) was significantly reduced in the O group ( p < 0.01) but was partially restored by exercise training. Histological analysis demonstrated a marked increase in myocardial fibrosis in the O group ( p < 0.001), which was significantly attenuated by exercise in the OE group ( p < 0.001). Conclusion Exercise training improved aerobic capacity, induced selective mitochondrial protein adaptations and attenuated myocardial fibrosis under oestrogen‐deficient conditions, supporting its potential as a non‐pharmacological intervention in postmenopausal settings.
ABSTRACT Background The gluteus maximus (GM) is a major hip extensor essential for mobility and metabolic health. Previous studies rely on global measures, such as muscle volume or fat fraction, which can overlook spatially localised differences in shape across the GM. Here, we integrate conventional volumetric and fat fraction metrics with 3D mesh‐based shape phenotypes to provide a spatially resolved characterisation of GM morphology in relation to anthropometric, lifestyle and cardiometabolic factors, with a focus on type 2 diabetes (T2D) and sex‐specific effects. Methods We analysed T1 Dixon MRI from UK Biobank participants to quantify GM muscle volume, fat fraction and regional surface morphology using 3D meshes. Statistical parametric mapping was used to assess regional associations with anthropometric, lifestyle and clinical variables. Statistical shape analysis was used to derive principal components (PCs) summarising major modes of GM shape variation, which were evaluated for associations with disease outcomes. Bidirectional causal mediation analyses were performed using GM volumetric and PCs of shape variation. Longitudinal changes in GM composition were assessed in participants with repeat imaging. Results GM muscle volume and fat fraction were strongly associated with age, adiposity and physical activity. Shape analysis identified spatially localised remodelling patterns that were not captured by global measures, revealing region‐specific surface shrinkage linked to age, BMI, alcohol intake, grip strength, physical activity, frailty, osteoporosis and cardiometabolic disease. T2D exhibited distinct sex‐specific patterns: Men showed predominantly inward deformation across the anterior and central GM, whereas women demonstrated outward deformation in corresponding anterior regions and throughout the posterior muscle, with several posterior regions significant only in women. Mediation analyses suggested that T2D‐related changes in GM morphology partly mediated increases in fat fraction, indicating that diabetes influences regional muscle shape beyond overall muscle size. PCs representing variation in the central‐superior posterior and anterior GM differentiated T2D cases from controls and were associated with incident T2D risk (men: left GM PC6 HR per SD 0.81 [0.70–0.95], false discovery rate [FDR]‐adjusted p = 0.038; right GM PC6 HR 0.76 [0.65–0.88], p = 0.002; women: right GM PC5 HR 1.32 [1.08–1.61], p = 0.032). Conclusions Integrating 3D GM morphology with conventional muscle composition measures identifies regional shape biomarkers that extend beyond muscle volume and fat fraction. These biomarkers capture spatially specific remodelling associated with anthropometric, lifestyle and cardiometabolic factors, providing improved insight into muscle–fat phenotypes and enhancing risk stratification in population‐based imaging studies.
ABSTRACT Background Sarcopenia, the progressive loss of skeletal muscle mass, and myosteatosis, the pathological fat infiltration into muscle tissue, are emerging prognostic factors in oncology. Both can be evaluated on computed tomography (CT). Despite advances in treating haematologic neoplasms, risk stratification remains challenging, and novel imaging biomarkers are needed. This systematic review and meta‐analysis investigated the prognostic impact of sarcopenia and myosteatosis on survival outcomes in patients with haematologic neoplasms. Methods The analysis was performed and reported in accordance with Cochrane and PRISMA guidelines. Literature searches were conducted in MEDLINE library, Cochrane, Web of Science and SCOPUS through January 2025. Eligible studies assessed sarcopenia or myosteatosis via CT in adult patients with non‐Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), multiple myeloma (MM), or leukaemia, across different clinical settings. Primary outcomes were overall survival (OS); secondary outcomes included progression‐free survival (PFS), and disease‐free survival (DFS), reported as hazard ratios (HRs) with 95% confidence intervals (CIs). Results Thirty‐four studies were included, comprising 5309 patients for sarcopenia (29 studies) and 2213 for myosteatosis (11 studies), with six studies assessing both conditions. The sample size‐weighted prevalence was 43.9% for sarcopenia (median 48.8%, range 10.0%–86.8%) and 41.9% for myosteatosis (median 42.6%, range 22.0%–73.7%). Among sarcopenia studies, 44.8% assessed patients undergoing chemotherapy‐immunotherapy, 24.1% in haematopoietic stem cell transplantation settings and 17.2% during chemotherapy. In NHL, sarcopenia was associated with reduced OS in multivariable analysis (HR 1.70, 95% CI 1.42–2.03, p < 0.001) and univariable analysis (HR 2.00, 95% CI 1.63–2.47, p < 0.001; I2 = 26%). Sarcopenia was associated with decreased PFS in NHL (multivariable HR 1.63, 95% CI 1.38–1.92, p < 0.001; I2 = 0%; univariable HR 1.76, 95% CI 1.52–2.04, p < 0.001; I2 = 0%). Myosteatosis was linked to inferior OS in NHL in multivariable analysis (HR 2.36, 95% CI 1.72–3.23, p < 0.001; I2 = 0%) and to reduced PFS (multivariable HR 1.62, 95% CI 1.25–2.10, p < 0.001; I2 = 0%; univariable HR 2.03, 95% CI 1.59–2.61, p < 0.001; I2 = 0%). Sarcopenia was associated with inferior OS in leukaemia (HR 1.82, 95% CI 1.39–2.36, p < 0.001) and worse PFS in leukaemia (HR 2.22, 95% CI 1.30–3.79, p = 0.004). Myosteatosis was linked to reduced OS in MM (HR 1.97, 95% CI 1.19–3.26, p = 0.008) and leukaemia (HR 2.67, 95% CI 1.74–4.09, p < 0.001). Conclusions CT‐based muscle assessment is independently associated with survival outcomes in selected haematologic neoplasms.
ABSTRACT Background Silent lacunar infarcts (SLIs) are asymptomatic subcortical infarcts detected on brain magnetic resonance imaging (MRI) and are associated with the risk of stroke and cognitive decline. The relationship between SLIs and physical performance and skeletal muscle mass in community‐dwelling older adults remains unclear. We examined whether SLI is associated with physical performance and muscle mass in older Japanese adults. Methods We conducted a cross‐sectional analysis of 1540 community‐dwelling adults aged 65–84 years from the Bunkyo Health Study with no prior stroke. SLIs were defined as 3‐ to 15‐mm infarcts on MRI and categorized as none, single or multiple. Physical performance was assessed using knee extensor and flexor strength, handgrip strength, maximum gait speed, two‐step test, the timed up and go (TUG) test and one‐leg standing test. Muscle mass was assessed using dual‐energy X‐ ray absorptiometry (DXA) derived appendicular skeletal muscle index (SMIht), body mass index (BMI) adjusted SMI (SMIBMI) and calf circumference. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). A multivariable linear regression model was used to analyse SLI as an ordinal variable (none, single or multiple) with multiple adjustments. Results Among 1540 participants (mean age: 73.0 ± 5.4; 58.8% female), 254 (16.5%) had SLIs. Among those with SLIs, 184 (72.4%) had multiple infarcts. Higher SLI burden was associated with older age, higher BMI and waist circumference, higher prevalence of hypertension and lower cognitive function (p for trend < 0.001). In adjusted analyses, increasing SLI burden was associated with lower knee extensor strength (B = −1.92 Nm, 95% confidence interval [CI] = −3.32 to −0.51, p = 0.008), lower knee flexor strength (B = −1.52 Nm, 95% CI = −2.39 to −0.65, p < 0.001), lower handgrip strength (B = −0.33 kg, 95% CI = −0.63 to −0.04, p = 0.029), slower maximum gait speed (B = −0.03 m/s, 95% CI = −0.05 to −0.01, p = 0.005), longer TUG time (B = 0.22 s, 95% CI 0.12–0.32, p < 0.001) and lower two‐step test performance (B = −0.02, 95% CI −0.03 to −0.01, p < 0.001). Higher SLI burden was also associated with lower SMIht (B = −0.04 kg/m2, 95% CI = −0.08 to −0.00, p = 0.047), lower SMIBMI (B = −0.01, 95% CI −0.01 to −0.00, p = 0.025) and smaller calf circumference (B = −0.18 cm, 95% CI −0.31 to −0.05, p = 0.006). Conclusions Among community‐dwelling older Japanese adults, greater SLI burden was independently associated with impaired physical performance and lower muscle mass. Further longitudinal studies are required to clarify temporal relationships and mechanisms.
ABSTRACT Aims Sarcopenia, the age‐related decline in skeletal muscle mass, strength and functionality, significantly contributes to frailty, falls and disability among older adults, resulting in increased morbidity, mortality and healthcare expenditures. As the global population ages and multimorbidity becomes more widespread, there has been growing interest in nutritional strategies to address sarcopenia. This comprehensive review highlights the current evidence regarding dietary supplements and nutraceuticals that support muscle health during aging, with particular emphasis on their efficacy, safety and interactions with resistance training. Methods An extensive review of literature from PubMed and Embase up to 2025 was conducted, including randomized controlled trials, meta‐analyses and mechanistic studies concerning creatine, amino acids, whey protein, collagen peptides, vitamin D, vitamin C, omega‐3 polyunsaturated fatty acids (PUFAs) and β‐hydroxy‐β‐methylbutyrate (HMB). Results Although exercise remains the fundamental intervention for managing sarcopenia, certain supplements can enhance anabolic responses when combined with physical training. Creatine and leucine‐enriched amino acids consistently increase lean mass and strength; whey protein supports muscle hypertrophy, particularly in individuals with low baseline protein intake. Vitamin D offers benefits to individuals with deficiencies, while omega‐3 PUFAs can moderately enhance physical function. Collagen peptides and HMB provide modest yet meaningful improvements when used adjunctively with resistance exercise. It is important to note that no supplement is effective as a sole intervention. Side effects are infrequent at recommended dosages; however, excessive vitamin D intake or high doses of fish oil may carry risks for some individuals. Conclusions Overall, a multifaceted approach combining resistance training and targeted nutritional supplementation is advocated to maintain muscle health during aging. Future large‐scale clinical trials are warranted to elucidate optimal combinations, dosages and patient populations most likely to benefit from such interventions.
ABSTRACT Background Statins are widely prescribed to reduce low‐density lipoprotein (LDL) cholesterol to decrease the risk of cardiovascular disease. However, there are ongoing concerns surrounding the frequently reported skeletal muscle side effects. These include muscle pain, weakness and reduced function and are defined as statin‐associated muscle symptoms (SAMS). This study aimed to characterise the biological processes, which underlie SAMS through analysing in vitro muscle cell phenotypic and transcriptomic effects of atorvastatin, the most prescribed statin, using human myoblasts from older adults. Methods Human myoblasts were isolated from vastus lateralis biopsies of 11 female older adult participants (average age 78.4 years) who were not on statin therapy from the Hertfordshire Sarcopenia Study extension (HSSe). Myoblasts were treated with 1, 5, or 10 μM atorvastatin for 4 days in proliferating or differentiating cultures. In proliferating cells, cytotoxicity, senescence and proliferation were measured using LDH cytotoxicity, β‐galactosidase (β‐gal) and 5‐ethynyl‐2′‐deoxyuridine (EdU) assays. To understand the influence of atorvastatin treatment across myoblast differentiation, immunocytochemistry (ICC) was undertaken analysing Myogenic Differentiation 1 (MyoD), Myogenin (MyoG) and Myosin Heavy Chain (MyHC). RNA sequencing (RNA‐seq) was performed on a subset of 10 differentiating myoblast cultures treated with 10 μM atorvastatin followed by gene ontology and protein–protein interaction (PPI) pathway analysis (Metascape). Results Atorvastatin treatment was not significantly toxic to myoblasts at any of the concentrations tested (1 μM p = 0.32, 5 μM p = 0.21 or 10 μM p = 0.76). Senescence increased with atorvastatin at 5 μM (p = 1.95 × 10−4) and 10 μM (p = 9.77 × 10−4). Myoblast proliferation decreased at all of 1 μM (p = 1.86 × 10−2), 5 μM and 10 μM (p = 9.77 × 10−4) concentrations. In differentiating cells, ICC identified MyoD significantly decreased with 10 μM atorvastatin; decreased MyoG at 1, 5, and 10 μM atorvastatin (p = 9.77 × 10−4); and decreased MyHC at 1 μM (p = 3.2 × 10−2), 5 μM (p = 2.93 × 10−3) and 10 μM atorvastatin (p = 1.37 × 10−2). RNA‐Seq analysis following 10 μM atorvastatin treatment in differentiating myoblast cultures revealed 822 genes upregulated and 888 genes downregulated in expression (false discovery rate [FDR] < 0.05). Pathway and MCODE analysis identified key networks downregulated, including muscle contraction and cell cycle process, and upregulated pathways implicated in cholesterol and fatty acid synthesis. Conclusions These findings show that atorvastatin treatment negatively impacts skeletal muscle at the cellular level by disrupting many key gene regulatory pathways involved in muscle maintenance, function and health. Identification of such disruption, which likely underpins SAMS, provides novel molecular mechanisms, which could be targeted through pharmaceutical/nutraceutical interventions to reduce the negative effects of statins on skeletal muscle health.
ABSTRACT Background Muscle atrophy is associated with many disease states and can become a debilitating and life‐threatening condition with few or no therapeutic options. The muscle‐specific E3 ligase muscle RING‐finger protein‐1 (TRIM63/MuRF1) has been identified as a promising target to treat muscle atrophy. Therapeutic evaluation of TRIM63 is hampered by challenges to target TRIM63 specifically while avoiding the closely related E3 ligases TRIM55/MuRF2 and TRIM54/MuRF3. Small interfering RNA (siRNA) technology can be used to generate specific reduction of messenger RNA (mRNA) transcripts, but delivery of sufficient concentrations of oligonucleotide‐based drugs to skeletal muscle has been challenging. We investigated an antibody‐oligonucleotide conjugate (AOC) combining the precision of siRNAs and the efficiency of receptor‐mediated delivery of oligonucleotides into skeletal muscle (specifically using a transferrin receptor 1 [TfR1] antibody [αTfR1]) to overcome these challenges and efficiently target TRIM63 in muscle. Methods Active Trim63 siRNAs were identified by screening in murine C2C12 myotubes and in vivo in wild‐type mice. A selected siRNA was then tested in two mouse models of muscle atrophy—hindlimb immobilization and denervation—to evaluate whether siTrim63 AOC can ameliorate muscle atrophy. Muscle weight was assessed at multiple time points to determine the impact of αTfR1 AOC administration. A primate‐cross‐reactive αTfR1 AOC was administered to cynomolgus monkeys to assess TRIM63 expression across species. Results We identified siTrim63 AOCs that reduced Trim63 expression in murine skeletal muscle by > 75% for 16 weeks, and > 50% for 6 months. In the hindlimb immobilization mouse model, siTrim63 AOC resulted in significantly reduced muscle weight loss of 10.1% (**p < 0.01) at 14 days post‐immobilization compared to 19.3% (****p < 0.0001) in the control‐treated leg. In the denervation model, siTrim63 AOC significantly reduced muscle weight loss to 38.9% (**p < 0.01) at 21 days post‐denervation compared to 55.0% (****p < 0.0001) in the control‐treated leg. We observed that siTrim63.22 AOCs led to 54% (****p < 0.0001) muscle sparing in denervated hindlimbs measured by leg cross‐section size. Treatment of non‐human primates (NHPs) with a siTRIM63 AOC reduced TRIM63 expression by 68% (average in two skeletal muscles). Conclusions Trim63/TRIM63 expression can be specifically reduced in skeletal muscle by siRNAs targeting Trim63/TRIM63 mRNA when administered systemically as an αTfR1 AOC in mice and NHPs. Our data support the therapeutic hypothesis that TRIM63 inhibition reduces muscle atrophy when administered at or near the time of insult. We provide evidence for the translatability of this strategy to primates.
ABSTRACT Background Muscular dystrophies (MD) are a genetically diverse group of muscle disorders, many of which arise from mutations in genes encoding components of the sarcolemma dystrophin‐associated glycoprotein complex (DGC). Despite their notorious heterogeneity, MDs consistently lead to chronic myofiber weakening, necrosis and loss of muscle mass, yet few unifying molecular pathways have been identified to explain this shared pathology. Methods In light of recent findings characterizing muscle symptoms in limb‐girdle MD recessive 28 (LGMDR28) – a condition caused by mutations to the rate‐limiting cholesterol synthesis enzyme and statin target 3‐hydroxy‐3‐methyl‐glutaryl‐coenzyme A reductase (HMGCR) – we summarize 4 decades of robust evidence describing how muscle ‘cholesterol depletion’ causes statin‐associated myopathies (SAM), which range from mild hyperCKmia to life‐threatening rhabdomyolysis during hypercholesterolemia management. After discussing myopathies caused by variants to 2 additional cholesterol pathway enzymes, we examine emerging data depicting circulating cholesterol abnormalities, muscle ‘cholesterol overload’ and lysosomal defects in multiple forms of rodent and human MD including Duchenne muscular dystrophy (DMD). Results When taken in combination with evidence showing extreme exacerbation of the notoriously mild phenotypes of dystrophin‐deficient mdx and dysferlin‐deficient mice by hypercholesterolemia, therapeutic responses to simvastatin and cholesterol absorption blocker ezetimibe in pre‐clinical studies, these findings suggest that multiple forms of MD may interfere with muscle cholesterol homeostasis to cause muscle wasting, akin to statins. Conclusions Further causal and mechanistic evidence of MDs being cholesterol‐handling diseases may ultimately lead to the counter‐intuitive testing of statins, ezetimibe and other cholesterol medications in certain MD populations and shed light on the muscle side‐effects of the most‐widely prescribed drug class.
ABSTRACT Sarcopenia, the age‐related decline in skeletal muscle mass and strength, is a growing public health concern, yet several meta‐analyses may be unreliable due to methodological and systemic challenges. This article examines issues compromising meta‐analytic validity: flexibility in study design and analysis, lack of control for parameters influencing muscle health, heterogeneity in definitions and measurements, epidemiological pitfalls, impact of comorbidities, and examination of sarcopenia combined with prolonged sedentary lifestyle. Specifically, flexible designs and p‐hacking may inflate spurious findings, while heterogeneity in definitions and measurement methods, often resulting in modest effect sizes, could challenge clinical interpretation. Publication bias may favour positive results, while epidemiological pitfalls, including reverse causality (e.g., sarcopenia as a consequence rather than the cause of conditions) and associative claims (e.g., gut microbiome correlations), may hinder causal inferences. Unadjusted comorbidities, heterogeneous interventions (e.g., combining heterogeneous therapies), comparators (e.g., placebo vs. usual care), and uncontrolled dietary intake and sleep quality may further obscure results. Sarcopenia‐based studies may also be confounded by lifelong sedentary behaviour, as lack of physical activity/exercise history could limit the isolation of age‐related sarcopenia from physical inactivity combined with age‐related sarcopenia. To enhance rigour in meta‐analyses in the field, standardized definitions, pre‐registered protocols, harmonized assessments, comorbidity phenotyping, intervention and comparator stratification, and causal inference techniques seem essential. Well‐controlled longitudinal studies tracking exercise history are warranted, whereas advanced statistical methods and data sharing could improve validity. Overall, these applications may help establish robust evidence to inform tailored clinical interventions and policy decisions for ageing populations.
ABSTRACT Introduction Progressive functional decline is a defining feature of cancer cachexia. We evaluated the effects of multicomponent interventions for adults with cancer cachexia on physical function outcomes. We also explored whether changes in physical function outcomes or overall quality of life varied following interventions with or without components directly targeting physical function (e.g., exercise training). Methods We analysed functional outcomes from studies included in our published systematic review of multicomponent interventions for adults with cancer cachexia, supplemented with an updated search. We conducted meta‐analyses of change scores from randomised trials comparing physical function outcomes following multicomponent interventions versus standard care. Exploratory analyses of standardised effect measures, including studies of any design, compared interventions based on whether or not they directly targeted physical function. Results We analysed data from 35 studies of multicomponent interventions, 19 of which included components directly targeting physical function. Handgrip strength was on average 1.06 kg greater (95% CI, −0.72–2.84 kg), and 6‐min walk distance was on average 16.20 m greater (95% CI, −38.27–70.67 m), following multicomponent intervention compared with standard care. Exploratory analysis showed improvement in fatigue was highest following an intervention with a specific fatigue self‐management component (standardised mean change: 4.76). Standardised mean change in quality of life was slightly lower following interventions with components directly targeting physical function (0.28 vs. 0.59) though effects were varied. Conclusions Multicomponent interventions appear to be superior to standard care for improving some measures of physical function for adults with cancer cachexia, namely, handgrip strength and the 6‐min walk distance. Interventions targeting specific aspects of physical function (e.g., fatigue) may lead to greater improvements in those outcomes.
ABSTRACT Background Although haematopoietic stem cell transplantation (HSCT) is known to cause substantial declines in muscle strength, changes in skeletal muscle quantity and quality remain poorly characterized. The clinical utility of non‐invasive muscle assessment tools, such as bioelectrical impedance analysis (BIA) and ultrasound (US) imaging, has not been systematically compared with computed tomography (CT), which is regarded as the gold standard for skeletal muscle assessment. Methods This study included 31 patients who underwent HSCT (23 allogeneic, 8 autologous; 42% female; median age 47 years). Skeletal muscle mass and quality were assessed using CT, BIA, and US imaging. CT was performed before transplantation, while BIA, US imaging, and physical performance assessments (handgrip strength, knee extension strength, and 6‐min walk test) were conducted both before transplantation and at discharge. Correlations between CT and non‐invasive assessments were analysed, and longitudinal changes in muscle parameters were evaluated. Results BIA‐derived skeletal muscle index and lower‐limb muscle mass showed strong correlations with CT‐based psoas muscle volume (ρ > 0.75, p < 0.001). CT‐based psoas muscle density demonstrated moderate correlations with phase angle and muscle echo intensity (ρ = −0.47 to 0.41, p < 0.05). In patients undergoing allogeneic HSCT, significant declines were observed in hydration‐adjusted lean body mass (mean change −2.1 kg, p = 0.024), lower‐limb muscle mass (−0.5 kg, p = 0.005) and rectus femoris + vastus intermedius thickness (−3.5 mm, p = 0.004), phase angle (−0.6°, p < 0.001), handgrip strength (−4.4 kg, p < 0.001), knee extension strength (−72.7 N, p < 0.001), and 6‐min walk distance (−93.7 m, p < 0.001). In contrast, patients undergoing autologous HSCT largely preserved muscle strength and mass (p > 0.200), despite similar reductions in phase angle (−0.6°, p = 0.001). Conclusions BIA provides a clinically feasible and reliable alternative to CT for assessing skeletal muscle quantity in patients undergoing HSCT. Loss of skeletal muscle mass was strongly associated with functional decline in recipients of allogeneic HSCT, while changes in muscle quality, such as reductions in phase angle, appeared to have limited functional impact. These findings highlight the usefulness of non‐invasive monitoring and suggest that interventions focusing on muscle mass preservation may improve physical function after HSCT.
To determine the associations between deficits in the visual function system, comprising visual acuity (VAI), contrast sensitivity (CSI), colour vision (CVI), depth perception (DPI) and visual field (VFI) impairments, as well as poor muscle health in an older Asian population. We used data from the baseline assessment of the Population Health and Eye Disease Profile in Elderly Singaporeans (PIONEER; 2017–2022) study. Visual function deficits included near visual acuity impairment (NVAI) (> N8), distance visual acuity impairment–DVAI (< 20/40 or > 0.3 logMAR), CSI (< 1.55 logCS), CVI (1 or more major crossings on Farnsworth D-15), DPI (≥ 150 arc sec) and VFI (Hodapp, Parish and Anderson criteria). Poor muscle health was defined as the presence of either low muscle mass (appendicular-lean-mass/height 2 of < 7 kg/m 2 for males and < 5.4 kg/m 2 for females), or low muscle strength (handgrip strength < 28 kg and < 18 kg, in men and women, respectively) or low physical performance (gait speed of < 1.0 m/s). Regression models were utilized to evaluate the associations between visual deficits and poor muscle health after adjusting for sociodemographic, clinical and lifestyle factors. Of the 2199 included participants (1105 Chinese, 580 Malays and 514 Indians; mean age ± SD: 72.9 ± 8.3 years; 54.3% female), 91.7% had poor muscle health. In multivariable analyses, DVAI (odds ratio [OR]: 2.01; 95%CI: 1.19, 3.40), NVAI (OR: 2.48; 95%CI: 1.31, 4.71), CSI (OR: 1.77; 95%CI: 1.18, 2.64) and CVI (OR: 1.95; 95%CI: 1.07, 3.59) were significantly associated with approximately twice the odds of poor muscle health. Moreover, the likelihood of poor muscle health significantly increased with the severity of visual function deficits (all p trend < 0.05). Participants with moderate–severe DVAI, NVAI, CSI and DPI had much higher odds (OR range: 2.24–5.78) of poor muscle health compared to those without these impairments. No associations were found between VFI and poor muscle health. The leading cause of VAI (near or distance) or CSI in those with poor muscle health was cataract (50.5%). Older adults with visual function deficits, especially moderate–severe impairment in DVAI, NVAI and CSI, have a much higher likelihood of poor muscle health. Importantly, most cases of VAI or CSI were treatable. These findings support targeted clinic-based assessment of visual function deficits and interventions (e.g., cataract surgery) as potential strategies for early prevention and management of poor muscle health.
Acute sarcopenia in hospitalised older adults is associated with poor outcomes, such as functional decline, increased risk of falls and prolonged hospital stays. Despite this, its development among older inpatients remains poorly understood. We aimed to quantify the effects of acute hospitalisation on sarcopenia outcomes in older adults. MEDLINE, EMBASE, CINAHL and Web of Science were searched from inception until January 2025. Studies that included acutely admitted patients aged 65 years or older and reported changes in at least one measure of sarcopenia during hospitalisation were included. Barthel Index was also included. A random-effects meta-analysis was undertaken. Fifty-five eligible studies were included, with a participant mean age of 82.2 years ( n = 14 919 participants). Our meta-analysis showed grip strength and chair-to-stand performance to significantly increase during hospitalisation (standard mean difference [SMD] = 0.06, 95% confidence interval [CI]: 0.00; 0.13, I 2 = 3%, p = 0.05 and SMD = 0.23, 95% CI: 0.13; 0.33, I 2 = 0%, p < 0.01, respectively). No physical performance measure showed a significant change. Muscle mass showed no change when measured by bioelectrical impedance analysis (SMD = 0.01, 95% CI: −0.09; 0.08, I 2 = 0%, p = 0.86). There were insufficient studies using MRI ( n = 2) or DEXA ( n = 1) to perform a meta-analysis. Individual studies showed a significant decrease in mid-thigh muscle area (cm 2 ) by MRI (mean difference [MD] = −3.9, p < 0.01) and a significant decrease in leg lean mass (kg) by DEXA (MD = −0.16, p < 0.05). Barthel Index score significantly increased from admission to discharge (SMD = 0.26, 95% CI: 0.06; 0.46, I 2 = 98.0%, p = 0.01) but significantly decreased from preadmission to discharge (SMD = −0.66, 95% CI: −0.92; −0.39, I 2 = 97.5%, p < 0.001). Both age and hospital length of stay had no effect on grip strength ( p = 0.615 and p = 0.096) or Barthel Index ( p = 0.835 and p = 0.279). This review has shown that grip strength improves during hospitalisation and decreases in muscle mass are observed when measured using MRI or DEXA. Muscle strength and physical performance assessed on admission are poor indicators of baseline status, as they are often adversely affected during acute illness, making them unrepresentative of true baseline capacity. The lack of improvement in physical performance outcomes is an important finding, as it represents failure to return to prehospital baseline abilities.
ABSTRACT Background Creatine supplementation (CrSUPP) has demonstrated benefits in improving body composition, muscle strength and physical function in healthy older adults. However, preclinical studies have raised concerns about the potential for CrSUPP to negatively impact cancer outcomes. This systematic review and meta‐analysis aimed to evaluate the efficacy and safety of CrSUPP in patients with cancer. Methods PubMed, Embase and Cochrane databases were systematically searched for randomized controlled trials (RCTs) comparing CrSUPP to placebo (PBO) in cancer patients. Outcomes included changes in body composition (lean mass [LM] and fat mass [FM]), muscle strength, physical function, quality of life (QoL), safety and survival. Standardized mean differences (SMD) or mean differences (MD) with 95% confidence intervals (CI) were calculated. Heterogeneity was assessed using the I2 statistic (significance: p < 0.1, I2 > 25%). Random‐effects models were applied. The protocol was registered in PROSPERO (CRD42025634948). Results Five RCTs including 373 patients (190 CrSUPP, 183 PBO) were analysed. Three studies included patients with non‐metastatic disease, whereas two included predominantly advanced cancer cases. Most patients were receiving active oncologic treatment. CrSUPP regimens varied, with three trials using a loading dose (20 g/day for 5–7 days), followed by maintenance (2–5 g/day), and two trials using either a loading or maintenance dosing strategy. Intervention duration ranged from 1 to 12 weeks, combined with resistance training in two studies. There were no significant differences between CrSUPP and PBO for LM (MD 0.55 kg [95% CI, −3.96, 5.07], p = 0.81, I2 = 0%) or muscle strength (SMD −0.05 [95% CI, −0.29, 0.18], p = 0.65, I2 = 0%). FM was significantly reduced in the CrSUPP group (MD −2.81 kg [95% CI, −4.21, −1.41], p < 0.001, I2 = 0.9%). Physical function showed no significant changes (SMD −0.20 [95% CI, −0.68, 0.28], p = 0.41, I2 = 0%). QoL was assessed in three studies, with data available from two, showing no CrSUPP effect. Safety data from three studies revealed no differences in adverse events between groups; renal function was assessed in one trial and showed non‐clinically relevant creatinine elevations. Overall survival was reported in one trial, showing no impact of CrSUPP. Conclusions CrSUPP did not significantly affect muscle strength, physical function or lean mass in cancer patients and may be associated with a reduction in fat mass; however, this finding should be interpreted with caution given the limited number of studies, heterogeneity of patient populations, interventions and outcome measures.
Muscle mass is an important determinant of clinical outcome in chronic diseases as well as in acute infectious diseases such as COVID-19. Both dual-energy x-ray absorptiometry (DXA) and computed tomography (CT) imaging are utilized to quantify muscle. The objective of this study was to assess the agreement between CT segmental analysis of muscle and whole-body muscle mass from DXA. A prospective observational study was carried out among COVID-19 survivors at least 1 year after the infection. The participants underwent a comprehensive multidimensional health assessment, including DXA and an extended chest CT. Lean mass (LM) and appendicular skeletal muscle mass (SMM) were derived from DXA, and pectoralis, L1 and L3 muscle cross-sectional area (CSA) were assessed using Slice-O-Matic software version 5.0 from the CT scans. Agreement between the two methods was assessed using Pearson correlation and Bland–Altman plots. One hundred thirty COVID-19 survivors (age 60.8 ± 13.1 years, female % 31.5, BMI 29.9 ± 5.2 kg/m 2 ) were included in the analysis. 83.9% of the participants were obese or overweight. Muscle CSA at L1 and L3 had a strong positive correlation with DXA LM and SMM (L1: r = 0.866 and r = 0.853 for LM and SMM, respectively; L3: r = 0.845 and r = 0.845, p < 0.001). Bland–Altman plots showed good agreement between the two methods. CT pectoralis showed a moderate correlation with DXA LM and SMM ( r = 0.659 and r = 0.684, respectively, p < 0.001). Muscle CSA at L1 and L3 from CT scans is strongly correlated, and pectoralis muscle CSA is moderately correlated with whole-body muscle mass measurement from DXA scans among COVID-19 survivors.
Preoperative evaluation of sarcopenia and nutritional status is a crucial prognostic factor in patients with gastrointestinal malignancies (GIM). Whole-body phase angle (Ph A), measured via bioelectrical impedance analysis (BIA), reflects cellular health and nutritional condition, and has gained attention as a potential prognostic marker. This study included 149 patients who underwent surgery for GIM at our department between April 2024 and May 2025. Sarcopenia was assessed using skeletal muscle index (SMI; men: < 7.0, women: < 5.7 kg m 2 ) derived from BIA, and those meeting the criteria were classified as ‘presumed sarcopenia (P-sarcopenia)’. Ph A values were also obtained using BIA, and skeletal muscle volume was measured using SYNAPSE VINCENT to determine the volume of large psoas muscle (PV). Among the 149 patients, 58 (38.9%) were diagnosed with P-sarcopenia, the breakdown being 31 males (53.4%) and 27 females (46.6%). The median age was 76 years (range: 53–89). Multivariate analysis revealed that low Ph A (odds ratio: 0.537, p < 0.04) and low PV (odds ratio: 0.992, p < 0.007) were significant risk factors for P-sarcopenia. These findings suggest that patients with P-sarcopenia tend to have lower Ph A and PV values. Patients with GIM who present with P-sarcopenia are more likely to exhibit reduced Ph A and PV, indicating compromised cellular and nutritional status. Ph A, as a non-invasive and easily obtainable parameter via BIA, may serve as a useful screening tool for identifying P-sarcopenia in preoperative settings.
Muscle weakness with age precedes muscle mass loss, and muscle quality is an issue in sarcopenia. Muscle tissue fibrosis progresses with age, with an increasing proportion of connective tissue containing collagen fibres. Increased fibrosis reduces the efficiency of force transmission during muscle contraction, leading to decreased muscle tension and overall performance. However, few studies have focused specifically on this condition and examined its treatment and effects. Using senescence-accelerated mouse-prone 8 (SAMP8) models, we aimed to clarify the effects of stretch stimulation on fibrosis and examine muscle function, histological changes in fibrosis and changes in fibrosis-related genes. The right side of the gastrocnemius muscle of 8-month-old SAMP8 was the stretch group and the left side the control group ( n = 8/group). The intervention was performed 15 times/min, 15 min/day and 5 days/week for 2 weeks. Muscle wet weight (MWW), ankle joint range of motion and passive/active tension were measured to evaluate muscle function. For histological analysis, muscle fibre cross-sectional area (CSA) and collagen content were calculated using haematoxylin and eosin and picrosirius-red staining, respectively. For molecular biological analysis, mRNA expression levels of fibrosis-related genes, transforming growth factor-β, α-smooth muscle actin (SMA), and collagen types I and III were measured using quantitative polymerase chain reaction. There was no significant difference in body weight and ankle joint's range of motion before and after the intervention. MWW after the intervention was higher in the stretch group (control group, 0.13 ± 0.01 g vs. stretch group, 0.14 ± 0.01 g; p < 0.05). No significant difference occurred in passive tension between groups; active tension was higher in the stretch group (control group, 2.98 ± 0.53 N/g vs. stretch group, 3.67 ± 0.52 N/g; p < 0.05). Histological findings showed a significantly higher CSA (control group, 2065.21 ± 93.98 μm 2 vs. stretch group, 2571.15 ± 187.12 μm 2 ; p < 0.05) and a significantly lower collagen content in the stretch group (control group, 1.28 ± 0.47% vs. stretch group, 0.53 ± 0.14%; p < 0.05). Thickening of the perimysium and endomysium was lower in the stretch group. Molecular biological findings showed a significant decrease in the expression levels of fibrosis-related genes, including α-SMA (control group, 1 ± 0.49 vs. stretch group, 0.30 ± 0.16; p < 0.05) and collagen type III (control group, 1 ± 0.39 vs. stretch group, 0.37 ± 0.23; p < 0.05). Stretching intervention in SAMP8 reduced the expression of some fibrosis-related genes, potentially contributing to a decrease in collagen proliferation in skeletal muscle and an increase in active tension.
High-speed resistance training has been shown to be a viable intervention for reducing neuromuscular symptoms in older persons with Parkinson's disease. Velocity-based training, a recently developed resistance training modality, utilizes velocity rather than load to dictate progressions. No study has examined the effects of this training method on muscle structure in Parkinson's patients. Sixteen older adults with Parkinson's disease (Hoehn and Yahr Stages 1–3) were randomly assigned to a 10% ( n = 7, 6 males, 1 female) or 30% ( n = 9, 6 males, 3 females) velocity loss threshold protocol twice weekly for 12 weeks of velocity-based training. Changes in ultrasound measures including muscle thickness, echo intensity, pennation angle, shear wave elastography, and performance measurements including specific force and power of the left and right rectus femoris and vastus lateralis were analysed before and after the intervention period. Significant improvements were seen for the sample in muscle thickness for the right (MDiff ± SE = 0.19 ± 0.05 cm; p = 0.003) and left (0.20 ± 0.09 cm; p = 0.033) rectus femoris and the right (0.14 ± 0.06 cm; p = 0.04) and left (0.19 ± 0.07 cm; p = 0.018) vastus lateralis. For echo intensity, there were significant improvements for the right rectus femoris (−3.37 ± 1.29 units; p = 0.002) and the left vastus lateralis (−7.11 ± 2.68 units; p = 0.019); however, improvements in the left ( p = 0.033) and right ( p < 0.001) vastus lateralis were seen only by the 30% velocity loss threshold group. Significant increases in pennation angle were detected in the right rectus femoris (2.47° ± 0.84°; p = 0.011) and reductions in shear wave elastography for the left rectus femoris (−3.33 ± 1.29 kPa; p = 0.013) of the sample. For specific power, significant improvements were seen for the right (0.02 ± 0.01 W·cm 3 ; p = 0.040) and left (0.04 ± 0.02 W·cm 3 ; p = 0.047) rectus femoris muscles for both groups. Results indicate that 12 weeks of velocity-based training can produce positive changes in muscle morphology and neuromuscular performance of the lower limbs for individuals with Parkinson's disease. Furthermore, using a 30% velocity loss threshold is more effective than using a 10% velocity loss threshold. Trial Registration: 20220489
