Muscle Mass Deficit Research Articles

Combined regenerative rehabilitation improves recovery following volumetric muscle loss injury in a rat model.

Volumetric muscle loss (VML) injury causes irreversible deficits in muscle mass and function, often resulting in permanent disability. The current standard of care is physical therapy, but it is limited in mitigating functional deficits. We have previously optimized a rehabilitation technique using electrically stimulated eccentric contraction training (EST) that improved muscle mass, strength, and size in VML-injured rats. A biosponge scaffold composed of extracellular matrix proteins has previously enhanced muscle function postVML. This study aimed to determine whether combining a regenerative therapy (i.e., biosponge) with a novel rehabilitation technique (i.e., EST) could enhance recovery in a rat model of VML. A VML defect was created by removing ~20% of muscle mass from the tibialis anterior muscle in adult male Lewis rats. Experimental groups included VML-injured rats treated with biosponge with EST or biosponge alone (n = 6/group). EST was implemented 2 weeks postinjury at 150 Hz and was continued for 4 weeks. A linear increase in eccentric torque over 4 weeks showed the adaptability of the VML-injured muscle to EST. Combining biosponge with EST improved peak isometric torque by ~52% compared with biosponge treatment alone at 6 weeks postinjury. Application of EST increased MyoD gene expression and the percentage of large (>2000 μm2) type 2B myofibers but reduced fibrotic tissue deposition in VML-injured muscles. Together, these changes may provide the basis for improved torque production. This study demonstrates the potential for combined regenerative and rehabilitative therapy to improve muscle recovery following VML.

Sarcopenia Prevalence among Hospitalized Patients with Severe Obesity: An Observational Study.

Background: Sarcopenic obesity (SO) is the combination of excess fat, skeletal muscle and muscular strength/function deficit. The ESPEN/EASO have proposed new diagnostic criteria, but the SO prevalence in patients with severe obesity remains to be established. The aim of this study was to establish the SO prevalence in a large cohort of inpatients with obesity, considering sex, age, BMI, type, and number of concomitant diseases. Methods: Patient data of both genders aged between 18 and 90 years with a body mass index (BMI) of ≥30 kg/m2 underwent hospital evaluation including bioelectrical impedance analysis (BIA) and handgrip strength (HS). QoL scores were obtained by the Psychological General Well-Being Index questionnaire. The study was approved by the institutional Ethic Committee. Results: Among the 3858 patients, 444 (11.51%) exhibited a strength deficit, while 3847 (99.71%) had skeletal muscle mass deficit. The prevalence of SO was then 11.48%, with higher rates in women (12.39%), in individuals aged >70 years (27%), and in those reporting a 'poor' QoL (12.6%). No significant difference in SO prevalence was found when stratifying by BMI (30-40 kg/m2 vs. >40 kg/m2, p = 0.1710). In SO patients, osteoarticular diseases (57%), hypertension/heart failure (38%), type 2 diabetes mellitus (34%), and obstructive sleep apnea (32%) were the more frequent comorbidities. Conclusions: The application of ESPEN/EASO-SO criteria in a cohort of inpatients with severe obesity revealed 11.48% SO prevalence, which was associated with age (particularly > 70 years), gender (women), but not BMI, as determinants. Disease staging and QoL screening may improve the identification of SO high-risk patients.

Resistance exercise training to improve post-operative rehabilitation in knee arthroplasty patients: A narrative review.

Knee osteoarthritis is associated with deficits in muscle strength, muscle mass, and physical functioning. These muscle-related deficits are acutely exacerbated following total knee arthroplasty (TKA) and persist long after surgery, despite the application of standardized rehabilitation programs that include physical/functional training. Resistance exercise training (RET) has been shown to be a highly effective strategy to improve muscle-related outcomes in healthy as well as clinical populations. However, the use of RET in traditional rehabilitation programs after TKA is limited. In this narrative review, we provide an updated view on whether adding RET to the standard rehabilitation (SR) in the recovery period (up to 1year) after TKA leads to greater improvements in muscle-related outcomes when compared to SR alone. Overall, research findings clearly indicate that both muscle strength and muscle mass can be improved to a greater extent with RET-based rehabilitation compared to SR. Additionally, measures of physical functioning that rely on quadriceps strength and balance (e.g., stair climbing, chair standing, etc.) also appear to benefit more from a RET-based program compared to SR, especially in patients with low levels of physical functioning. Importantly though, for RET to be optimally effective, it should be performed at 70%-80% of the one-repetition maximum, with 3-4 sets per exercise, with a minimum of 3 times per week for 8weeks. Based upon this narrative review, we recommend that such high-intensity progressive RET should be incorporated into standard programs during rehabilitation after TKA.

Initial stroke severity and discharge outcome in patients with muscle mass deficit.

This study aimed to investigate the association between muscle mass deficit and the initial severity of ischemic stroke. The impact of muscle mass deficit on the discharge outcome was also evaluated. This retrospective study included 660 patients with acute ischemic stroke who underwent bioelectrical impedance analyses. We compared the National Institute of Health Stroke Scale (NIHSS) score, occurrence of moderate stroke (NIHSSS ≥ 5) at admission, and unfavorable functional outcome (modified Rankin Scale score ≥ 2) at discharge between patients with and without muscle mass deficit using Poisson and logistic regression analyses. The mean age of the study patients was 65.6 ± 13.0, and 63.3% were males. Muscle mass deficit was present in 24.4% of patients. Muscle mass deficit was significantly and independently associated with NIHSS score or moderate stroke (all p < 0.05). This association was noted regardless of patient characteristics. Among the respective NIHSS items, muscle mass deficit was significantly associated with facial palsy, motor function of the arm or leg, limb ataxia, and dysarthria. Muscle mass deficit also led to unfavorable functional outcome, which was mediated by the initial NIHSS score. In conclusion, muscle mass deficit is associated with higher NIHSS score and unfavorable functional outcome in patients with acute ischemic stroke.

Association between Muscle Mass Deficits and Metabolic Dysfunction-Associated Fatty Liver Disease in Adults with Body Mass Index Less than 23 kg/m2

Association between Muscle Mass Deficits and Metabolic Dysfunction-Associated Fatty Liver Disease in Adults with Body Mass Index Less than 23 kg/m²

Skeletal muscle-focused guideline development: hierarchical model incorporating muscle form, function, and clinical outcomes.

Sarcopenia, sarcopenic obesity, malnutrition, and cachexia clinical guidelines were created by expert consensus over the past decade. These pathological states all share in common deficits in skeletal muscle mass, and in some cases muscle function, which adversely impact patient outcomes. Early identification is key as some detrimental outcomes are potentially preventable with available treatments. The four guidelines share common design features: patients suspected of having the condition are first screened with a focused clinical history; if positive, the next step is evaluation with either a measure of body "form" (e.g., mass, shape, and composition) or function (e.g., mechanical, endurance, and metabolic); combined form and functional criteria are also recognized. The form and functional "gateway" nodes establish whether or not to proceed with further evaluations and treatments. Intensive discussions among experts focus on selection of these gateway nodes and the final choice is made when consensus is reached. Form and functional measures are often treated as equivalent alternatives when framed in the context of "outcomes" for which they are intended to predict. Here we adapt a classic biological concept stating that "function follows form" to show that pathophysiological links are present between these two different muscle qualities and clinical outcomes. We argue that a hierarchy exists such that outcomes closely follow functions that, in turn, follow form…the OFF rule. The OFF rule explains why functional measures often show stronger associations with outcomes than those quantifying form, helps to frame debates on how to structure the gateway nodes used to identify patients for further evaluation and treatment, and sets out a pathophysiological structure for developing future outcome prediction models.

Malnutrition Patterns in Children with Chronic Kidney Disease

Malnutrition is frequent in children with chronic kidney disease (CKD). Apart from undernutrition and protein energy wasting (PEW), overnutrition prevalence is rising, resulting in fat mass accumulation. Sedentary behavior and unbalanced diet are the most important causal factors. Both underweight and obesity are linked to adverse outcomes regarding renal function, cardiometabolic risk and mortality rate. Muscle wasting is the cornerstone finding of PEW, preceding fat loss and may lead to fatigue, musculoskeletal decline and frailty. In addition, clinical data emphasize the growing occurrence of muscle mass and strength deficits in patients with fat mass accumulation, attributed to CKD-related wasting processes, reduced physical activity and possibly to obesity-induced inflammatory diseases, leading to sarcopenic obesity. Moreover, children with CKD are susceptible to abdominal obesity, resulting from high body fat distribution into the visceral abdomen compartment. Both sarcopenic and abdominal obesity are associated with increased cardiometabolic risk. This review analyzes the pathogenetic mechanisms, current trends and outcomes of malnutrition patterns in pediatric CKD. Moreover, it underlines the importance of body composition assessment for the nutritional evaluation and summarizes the advantages and limitations of the currently available techniques. Furthermore, it highlights the benefits of growth hormone therapy and physical activity on malnutrition management.

Age-Related Dysfunction in Proteostasis and Cellular Quality Control in the Development of Sarcopenia

Sarcopenia is a debilitating skeletal muscle disease that accelerates in the last decades of life and is characterized by marked deficits in muscle strength, mass, quality, and metabolic health. The multifactorial causes of sarcopenia have proven difficult to treat and involve a complex interplay between environmental factors and intrinsic age-associated changes. It is generally accepted that sarcopenia results in a progressive loss of skeletal muscle function that exceeds the loss of mass, indicating that while loss of muscle mass is important, loss of muscle quality is the primary defect with advanced age. Furthermore, preclinical models have suggested that aged skeletal muscle exhibits defects in cellular quality control such as the degradation of damaged mitochondria. Recent evidence suggests that a dysregulation of proteostasis, an important regulator of cellular quality control, is a significant contributor to the aging-associated declines in muscle quality, function, and mass. Although skeletal muscle mammalian target of rapamycin complex 1 (mTORC1) plays a critical role in cellular control, including skeletal muscle hypertrophy, paradoxically, sustained activation of mTORC1 recapitulates several characteristics of sarcopenia. Pharmaceutical inhibition of mTORC1 as well as caloric restriction significantly improves muscle quality in aged animals, however, the mechanisms controlling cellular proteostasis are not fully known. This information is important for developing effective therapeutic strategies that mitigate or prevent sarcopenia and associated disability. This review identifies recent and historical understanding of the molecular mechanisms of proteostasis driving age-associated muscle loss and suggests potential therapeutic interventions to slow or prevent sarcopenia.

The year in cardiovascular medicine 2022: the top 10 papers in arrhythmias.

(A) Comprehensive clinical, electrocardiographic, and genetic overview of the various diseases associated with VA or SCD as reported in the 2022 ESC Guidelines for VA and SCD.1 The VA/SCD Guidelines provide many updated recommendations for the management of patients with congenital heart disease, idiopathic VF, acquired Long QT, Brugada and early repolarization syndrome, as well as catecholaminergic polymorphic VT, and short QT syndrome. (B) From the same Guidelines, an algorithm for the management of sustained monomorphic ventricular tachycardia in patients with chronic coronary artery disease.1 The algorithm also holdsin partfor non-ischaemic pathologies. Note, the new VA/SCD Guidelines promote VT ablation significantly. It may e.g. be performed to ameliorate or avoid ICD therapy, or to enhance resynchronization therapy by ablation of frequent monomorphic PVCs (extrasystolopathy). The trials PARTITA, PAUSE-SCD, and SURVIVE-VT, discussed in the present paper, all strengthen the recommendations for application of catheter ablation.57 (C) Exercise causes downregulation of genes coding intercalated disk proteins, as well as scaffolding and ion channel proteins, both in normal mice and PKP2 conditional knockouts. Consistent with PKP2-dependent muscle mass deficit, cardiac dimensions in human athletes carrying PKP2 mutations were reduced (data not shown), compared with matched controls. Exercise challenges a cardiomyocyte desmosomal reserve which, if impaired genetically (e.g. Plakophilin2 loss), can cause accelerated progression of the cardiomyopathy.3 Reprinted with permission.

STEP-HI Study: A Multimodal Intervention of Exercise and Testosterone Therapy: Design and Real-World Challenges

Hip fractures are common among older women and can have a devastating impact on their ability to remain independent. Many women who were high functioning before the hip fracture do not return to their pre-fracture level of function, have persistent weakness and mobility impairments, and may require ongoing supportive services. Age-associated androgen deficiency may contribute to deficits in muscle mass, strength and power that are common in older female hip fracture patients. The Starting a Testosterone and Exercise Program after Hip Injury (STEP-HI ) Study is a three-group, randomized, double-blinded, placebo-controlled Phase III clinical trial designed to evaluate a multi-modal intervention aimed at improving functional outcomes in older female hip fracture patients. 168 female hip fracture patients, age 65 yrs. and older are being recruited from 6 clinical sites in the USA. Participants are being assigned to one of three groups: supervised exercise (EX) plus 1% testosterone topical gel; EX plus placebo gel; or enhanced usual care. The primary outcome is six-minute walk distance. This symposium will present information related to key aspects of the design of the STEP-HI trial, including recruitment of a frail patient population during a period of injury recovery, the testosterone and exercise interventions and related fidelity procedures, and implementation challenges for this multi-modal intervention prior to and during the COVID-19 pandemic. In addition, the underlying mechanisms by which testosterone and exercise are expected to have a synergistic effect on muscle strength and function will be discussed.

Role of plakophilin-2 expression on exercise-related progression of arrhythmogenic right ventricular cardiomyopathy: a translational study.

Exercise increases arrhythmia risk and cardiomyopathy progression in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients, but the mechanisms remain unknown. We investigated transcriptomic changes caused by endurance training in mice deficient in plakophilin-2 (PKP2cKO), a desmosomal protein important for intercalated disc formation, commonly mutated in ARVC and controls. Exercise alone caused transcriptional downregulation of genes coding intercalated disk proteins. The changes converged with those in sedentary and in exercised PKP2cKO mice. PKP2 loss caused cardiac contractile deficit, decreased muscle mass and increased functional/transcriptomic signatures of apoptosis, despite increased fractional shortening and calcium transient amplitude in single myocytes. Exercise accelerated cardiac dysfunction, an effect dampened by pre-training animals prior to PKP2-KO. Consistent with PKP2-dependent muscle mass deficit, cardiac dimensions in human athletes carrying PKP2 mutations were reduced, compared to matched controls. We speculate that exercise challenges a cardiomyocyte "desmosomal reserve" which, if impaired genetically (e.g., PKP2 loss), accelerates progression of cardiomyopathy.

Association between Muscle Mass Deficits and the Non-Alcoholic Fatty Liver Disease Fibrosis Score in Adults without Central Obesity

Association between Muscle Mass Deficits and the Non-Alcoholic Fatty Liver Disease Fibrosis Score in Adults without Central Obesity

Prevalência de sarcopenia e fatores associados em pacientes submetidos a hemodiálise em um ambulatório em Caxias do Sul/RS

Introduction: The patients with chronic kidney disease (CKD) undergoing hemodialysis in most of the cases present low weight associated with muscle mass deficit and low physical performance, also had been diagnosed with sarcopenia. Within the main factors that lead to such outcome, we highlight the hypercatabolism of the disease and the uremic syndrome. The presence of sarcopenia can lead to associated with high mortality rates. The present study aims to evaluate the sarcopenia prevalence and relate factors of hemodialysis on former of clinic patients at Caxias do Sul/RS city. Methods: Anthropometric data collected, such as weight height and age for subsequent calculation and classification of body mass index (BMI), calf circumference (CC), handgrip strength and walking test for sarcopenia diagnosis. Sarcopenia is defined according to criteria pre-established by the European Working Group on Sarcopenia in Older People (EWGSOP). Results: 95 patients evaluated, 21% (n = 20) had sarcopenia, and 36.8% (n = 35) of the subjects were at risk for its development. Regarding the sample characterization, 61.1% (n = 20) were male, 53.7% (n = 51) were &lt;60 years old. The average age found was 55.4 ± 15.1 years. The mean BMI was 25.9 ± 5.1 kg/m², and 45.3% (n = 43) were overweight, 34.7% (n = 3) showed CC indicating muscle depletion. Conclusion: The conditions of probable sarcopenia and sarcopenia were present in most patients studied, especially in older and underweight patients.

ANTHROPOMETRIC AND DIETARY ASSESSMENT OF PATIENTS WITH GLYCOGENOSIS TYPE I.

ABSTRACTObjective: To perform anthropometric and dietary evaluation of patients with glycogenosis type Ia and Ib.Methods: This cross-sectional study is composed of a sample of 11 patients with glycogenosis divided into two subgroups according to the classification of glycogenosis (type Ia=5 and type Ib=6), aged between 4 and 20 years. The analyzed anthropometric variables were weight, height, body mass index, and measures of lean and fat body mass, which were compared with reference values. For dietary assessment, a food frequency questionnaire was used to calculate energy and macronutrients intake as well as the amount of raw cornstarch consumed. Mann-Whitney U test and Fisher’s exact test were performed, considering a significance level of 5%.Results: Patients ingested raw cornstarch in the amount of 0.49 to 1.34 g/kg/dose at a frequency of six times a day, which is lower than recommended (1.75-2.50 g/kg/dose, four times a day). The amount of energy intake was, on average, 50% higher than energy requirements; however, carbohydrate intake was below the adequacy percentage in 5/11 patients. Short stature was found in 4/10 patients; obesity, in 3/11; and muscle mass deficit, in 7/11. There were no statistical differences between the subgroups.Conclusions: In patients with glycogenosis type I, there was deficit in growth and muscle mass, but no differences were found between the subgroups (Ia and Ib). Although the diet did not exceed the adequacy of carbohydrates, about 1/3 of the patients presented obesity, probably due to higher energy intake.

Deficits in growth, muscle mass, and body composition following placental insufficiency-induced intrauterine growth restriction persisted in lambs at 60 d of age but were improved by daily clenbuterol supplementation.

Deficits in growth, muscle mass, and body composition following placental insufficiency-induced intrauterine growth restriction persisted in lambs at 60 d of age but were improved by daily clenbuterol supplementation.

258 Deficits in growth, muscle mass, and body composition following intrauterine growth restriction persisted in lambs at 60 d of age but were improved by daily clenbuterol supplementation

Abstract Intrauterine growth restriction (IUGR) reduces neonatal muscle growth and alters body composition in livestock. Our objective was to determine the effect of IUGR on juvenile growth and assess the benefits of treatment with clenbuterol (β2 adrenergic agonist) in IUGR offspring. Heat stress-induced IUGR lambs were born 28% lighter (P &amp;lt; 0.05) than controls. At 60 d of age, unsupplemented IUGR lambs had reduced (P &amp;lt; 0.05) bodyweight (BW), average daily gain, and crown-rump length compared to controls, but clenbuterol-supplemented IUGR lambs did not differ from controls. Crown circumference, body girth, and cannon bone length did not differ among groups. Bioelectrical impedance in live lambs and carcasses estimated that lean mass and mass of multiple muscle groups were reduced (P &amp;lt; 0.05) in unsupplemented IUGR lambs but not clenbuterol-supplemented IUGR lambs compared to controls. Estimated protein, fat, and protein/fat were likewise reduced (P &amp;lt; 0.05) in unsupplemented but not clenbuterol-supplemented IUGR lambs. Loin-eye area in chilled carcasses was 30% smaller (P &amp;lt; 0.05) in unsupplemented IUGR lambs but 19% larger (P &amp;lt; 0.05) in clenbuterol-supplemented IUGR lambs compared to controls. Proximate analysis revealed greater (P &amp;lt; 0.05) fat and reduced (P &amp;lt; 0.05) protein and protein/fat in loin muscles from unsupplemented but not clenbuterol-supplemented IUGR lambs compared to controls. At necropsy, hindlimbs, hearts, and flexor digitorum superficialis muscles tended to be lighter (P ≤ 0.09) and lungs and kidneys were lighter (P &amp;lt; 0.05) in IUGR lambs. Kidney weight was further reduced (P &amp;lt; 0.05) in clenbuterol-supplemented IUGR lambs. Brain/BW tended to be reduced (P ≤ 0.09) and lung/BW and kidney/BW were reduced (P &amp;lt; 0.05) in IUGR lambs, but lung weight and lung/BW were greater (P &amp;lt; 0.05) in clenbuterol-supplemented compared to unsupplemented IUGR lambs. We conclude that poor growth and asymmetric body composition previously observed in IUGR neonates persists in juveniles, but daily treatment with clenbuterol recovered growth and improved body composition in IUGR lambs.

Levantamento do estado nutricional e de complicações associadas à terapia nutricional enteral domiciliar em idosos

Introduction: The high prevalence of noncommunicable diseases (NCDs) and neurodegenerative diseases in elderly has been increasing the hospitalizations risk and, consequently, the malnutrition risk, which leads to a greater need for enteral tube feeding (ETF). Thus, this article aims to conduct a survey about nutritional status and complications related to home enteral tube feeding (HETF) in elderly. Methods: This is a descriptive observational study conducted in a medium-sized municipality of Greater São Paulo (Metropolitan region). To collect data, a survey of medical records and home visits was carried out from January 2012 to April 2018. Patients aged 60 years and over who had information on bowel habits, presence of pressure ulcers, position of feeding tube and anthropometric data of calf circumference (CC) and arm circumference (AC) were eligible. The values found for CC and AC were interpreted according to the reference cut-off points. Results: The study included 43 elderly people, 67.4% female and 32.6% male. The nasogastric feeding tube was present in 62,8% of the patients. Pressure ulcer was the most prevalent (58.1%) complications associated with HETF. Diarrhea was present in 4.7% of the elderly and constipation in 44.2%. In regard of nutritional status, muscle mass depletion was present in 88.4% of the elderly and severe mass deficit in 62.9% of them. Conclusions: The assessment of the nutritional status and complications associated with HETF in elderly showed that more than a half had some muscle mass deficit and the pressure ulcer was the most prevalent complication, followed by constipation and diarrhea.

Tracheostomy Post Liver Transplant: Predictors, Complications, and Outcomes

BackgroundLiver transplant (LT) patients have an increased risk of postoperative respiratory failure requiring tracheostomy. This study sought to characterize objective clinical predictors of tracheostomy.Material/MethodsThe records for 2017 LT patients at a single institution were reviewed. Patients requiring tracheostomy were first compared with all other patients. A case-control subgroup analysis was conducted in which 98 tracheostomy patients were matched with 98 non-tracheostomy LT patients. For the case-control study, muscle mass was assessed using preoperative computed tomography scans.ResultsAmong 2017 LT patients, 98 required tracheostomy (5%), with a 19% complication rate. Tracheostomy patients were older and had a higher model for end-stage liver disease score, a lower body mass index (BMI), and a greater smoking history. Tracheostomy patients had a longer hospital stay (45 vs. 10 days, P<0.001) and worse 1-year survival (65% vs. 91%, P<0.001). Ten-year Cox regression patient survival for tracheostomy patients was significantly worse (32% vs. 68%, P<0.001). In the case-control analysis, respiratory failure patients were older (P<0.01) and had a lower BMI (P=0.05). They also had a muscle mass deficit of −39% compared with matched LT controls (P<0.001). No significant differences were seen with pre-LT total protein or albumin or with forced expiratory volume in 1 s divided by forced vital capacity (FEV1/FVC) values.ConclusionsPredictors for respiratory failure requiring post-LT tracheostomy include higher model for end-stage liver disease score, older age, lower BMI, greater smoking history, and worse sarcopenia. Patients requiring tracheostomy have dramatically longer hospital stays and worse survival.

Characteristics of the metabolic status of children of the first year of life with protein-energy deficiency depending on the gestational age at birth.

Comparative analysis of energy-plastic exchange indicators in mature and premature children of the first year of life in the development of protein-energy malnutrition (PEM) was carried out. Unidirectional changes are revealed, including an increase in creatinine, lactate and creatine phosphokinase activity levels, suggesting a n increasing muscle mass deficit against the background of glucose anaerobic oxidation activation. In preterm infants, glucose and triacylglicerine levels decrease, which reflects uncompensated insufficiency of energy substrates and, accordingly, ATP level. Multidirectional deviations in metabolism are pyruvate and ATP content: increase in full-term infants and decrease in preterm infants, that should be taken into account when monitoring condition of children with PEM. A significant decrease of pyruvic acid in preterm infants against the background of the levels of total protein, albumin, hemoglobin, and transferrin, not exceeding reference values, can obviously testify to the active use of this integral metabolite to maintain the fund of substituted amino acids. Development of this pathology in both mature and premature infants creates a pre-morbid background for iron deficiency anemia-diagnostic panel, which should be supplemented by calculation of transferrin saturation coefficient. Regardless of gestational age in childbirth during the formation of PEM, the lipid spectrum is rearranged according to atherogenic type: at normal values of total cholesterol, there is a significant increase in low and very low density lipoproteins with an increase in the atherogenicity coefficient. This singles out children with the pathology in question as a risk group for the development of the atherosclerotic process later, which justifies the recommendation to control the lipid profile in children of the first year of life.

The Contribution of Environment to Impair Re‐Innervation in Age‐Related Failure of Muscle Regeneration Following Injury

An age‐related decline in the structure and function of the neuromuscular junction (NMJ) has been hypothesised to play an important role in the loss of muscle mass and force generating capacity that occurs during ageing and to contribute to the incomplete regeneration of skeletal muscle following damage.The aim of this study was to determine the relative levels of innervation of muscle fibres from adult and old wild type (WT) mice and in mice lacking superoxide dismutase (SOD1) SodKO mice prior to and during regeneration following extensive muscle damage induced by barium chloride (BaCl2). Based on the known role of environment as a contributor to the success of muscle regeneration, an additional aim was to test whether the deficits in innervation, muscle mass, and force generation seen in muscles of old mice was evident in muscles transplanted from old donors into adult hosts and vice versa.Male B6.Cg‐Tg (Thy1‐YFP) mice aged 8–10 months (adult) or 24 months (old), male adult (8–10 months) mice lacking SOD1 (C57Bl/6 Sod1KO mice) and male adult SOD1KO mice crossed with Thy1‐CFP (SOD1KO‐CFP) were used for the BaCl2 study. Mice were anaesthestised and the extensor digitorum longus (EDL) muscle was injected with 50ul BaCl2, (1.2% wt/vol in sterile saline). Adult and old WT mice were allowed to recover for up to 60 days. SOD1KO mice were studied prior to‐ and at 28 days post damage, the time point where failure in recovery of contractile force was seen in old WT mice.Male WT adult (6–8 months) and old (22 – 24 months) mice were used for the muscle transplant studies. EDL muscles were transferred to the new host, where the tendons were hen repaired and the nerve from the host implanted into the transplanted muscle. At 28 and 60 days following transplantation, mice were culled and EDL muscles were removed, contractile function measured and NMJ structure examined.For analysis of NMJ structure the post‐synaptic regions of fixed EDL muscles were stained with alpha‐bungarotoxin and Dapi. Multiple images were collected from each muscle and the innervation status of each NMJ was assessed.Data demonstrated that although the 30% full denervation of NMJ structure in association with some reduction in fibre diameter may be responsible for the 35% muscle force deficit that occurred in mice that lack SOD1, the level of denervation could not solely explain the substantial force deficit in muscle from old WT mice following extensive damage and regeneration. In contrast, data support the conclusion that the deficit in force seen in muscles from old WT mice following regeneration from damage is caused by the environment in which the muscle regenerated since transplantation of EDL muscles from either adult or old mice into old mice leads to defective regeneration of those muscles; however, experiments aimed at determining whether the environment impacted the effectiveness of re‐innervation remained inconclusive with substantial disruption evident in all instances.Support or Funding InformationWith thanks to National Institute of Ageing (AG051442) and University of Liverpool for their support.