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Background: Motor units (MUs) control the contraction of muscles and degenerate with age. It is therefore of interest to measure whole muscle and MU twitch profiles in aging skeletal muscle., Purpose: Apply phase contrast MU MRI (PC-MUMRI) in a cohort of healthy adults to measure whole anterior compartment, individual muscles, and single MU twitch profiles in the calf. Assess the effect of age and sex on contraction and relaxation times., Study Type: Prospective cross-sectional study., Subjects: Sixty-one healthy participants (N = 32 male; age 55 ± 16 years [range: 26-82])., Field Strength/sequences: 3 T, velocity encoded gradient echo and single shot spin echo pulsed gradient spin echo, echo-planar imaging., Assessment: Anterior shin compartment (N = 47), individual muscle (tibialis anterior, extensor digitorum longus, peroneus longus; N = 47) and single MU (N = 34) twitch profiles were extracted from the data to calculate contraction and relaxation times., Statistical Tests: Multivariable linear regression to investigate relationships between age, sex and contraction and relaxation times of the whole anterior compartment. Pearson correlation to investigate relationships between age and contraction and relaxation times of individual muscles and single MUs. A P value <0.05 was considered statistically significant., Results: Age and sex predicted significantly increased contraction and relaxation time for the anterior compartment. Females had significantly longer contraction times than males (females 86 ± 8 msec, males 80 ± 9 msec). Relaxation times were longer, not significant (females 204 ± 36 msec, males 188 ± 34 msec, P = 0.151). Contraction and relaxation times of single MUs showed no change with age (P = 0.462, P = 0.534, respectively)., Date Conclusion: Older participants had significantly longer contraction and relaxation times of the whole anterior compartment compared to younger participants. Females had longer contraction and relaxation times than males, significant for contraction time., Evidence Level: 2 TECHNICAL EFFICACY: Stage 1., (© 2023 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Sarcopenia is a progressive and generalized disease, more common in older adults, which manifests as a loss of muscle strength and mass. The pathophysiology of sarcopenia is still poorly understood with many mechanisms suggested. Age associated changes to the neuromuscular architecture, including motor units and their constituent muscle fibres, represent one such mechanism. Electromyography can be used to distinguish between different myopathies and produce counts of motor units. Evidence from electromyography studies suggests that with age, there is a loss of motor units, increases to the sizes of remaining units, and changes to their activity patterns. However, electromyography is invasive, can be uncomfortable, does not reveal the exact spatial position of motor units within muscle and is difficult to perform in deep muscles. We present a novel diffusion-weighted magnetic resonance imaging technique called 'motor unit magnetic resonance imaging (MUMRI)'. MUMRI aims to improve our understanding of the changes to the neuromuscular system associated with ageing, sarcopenia and other neuromuscular diseases. To date, we have demonstrated that MUMRI can be used to detect statistically significant differences in fasciculation rate of motor units between (n = 4) patients with amyotrophic lateral sclerosis (mean age ± SD: 53 ± 15) and a group of (n = 4) healthy controls (38 ± 7). Patients had significantly higher rates of fasciculation compared with healthy controls (mean = 99.1/min, range = 25.7-161.0 in patients vs. 7.7/min, range = 4.3-9.7 in controls; P < 0.05. MUMRI has detected differences in size, shape, and distribution of single human motor units between (n = 5) young healthy volunteers (29 ± 2.2) and (n = 5) healthy older volunteers (65.6 ± 14.8). The maximum size of motor unit territories in the older group was 12.4 ± 3.3 mm and 9.7 ± 2.7 mm in the young group; P < 0.05. MUMRI is an entirely non-invasive tool, which can be used to detect physiological and pathological changes to motor units in neuromuscular diseases. MUMRI also has the potential to be used as an intermediate outcome measure in sarcopenia trials., (© 2020 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Decline in skeletal muscle strength and mass (sarcopenia) accelerates with age, leading to adverse health outcomes and poor quality of life. Diet plays a crucial role in muscle ageing being an important element of a healthy lifestyle. However, unlike single nutrients, such as dietary protein, or dietary patterns, such as the Mediterranean diet, the relationship between individual whole foods and muscle health has not been systematically evaluated. We aimed to investigate which whole foods (meat, fish, eggs, fruit and vegetables, and non-liquid dairy) may be beneficial (myoprotective) for ageing muscle and sarcopenia in adults aged ≥ 50 years. Nineteen observational and nine intervention studies were identified through systematic searches of the four electronic databases (last search: March 2020). The synthesis of findings showed strong and consistent evidence for a beneficial effect of lean red meat on muscle mass or lean tissue mass in both observational and intervention studies. Higher intake of fruit and vegetables was associated with better muscle function in observational studies, but the evidence from intervention studies was scarce. Non-liquid dairy foods were beneficial for muscle mass in both observational and intervention studies. There was moderate evidence for the role of these foods in muscle strength and sarcopenia, and limited or inconclusive evidence for the benefits of other whole foods (e.g., fish, eggs) for muscle health in older adults. Although current nutritional recommendations are often based on a single nutrient approach, further research about the role of protein-rich and other foods in muscle health will allow for the development of guidelines that are based on whole foods, also highlighting the potential importance of non-protein nutrients within these foods for myoprotection in older adults.

Skeletal muscle aging manifests as a decline in muscle quantity and quality that accelerates with aging, increasing the risk of sarcopenia. Sarcopenia is characterized by a loss of muscle strength and mass, and contributes to adverse health outcomes in older adults. Intervention studies have shown that sarcopenia may be treated by higher protein intake in combination with resistance exercise (RE). In comparison, less is known about the role of whole protein-containing foods in preventing or treating sarcopenia. Liquid milk contains multiple nutrients and bioactive components that may be beneficial for muscle, including proteins for muscle anabolism that, alone or with RE, may have myoprotective properties. However, there is a lack of evidence about the role of milk and its effects on muscle aging. This narrative review considers evidence from three observational and eight intervention studies that used milk or fortified milk, with or without exercise, as an intervention to promote muscle health and function in older adults (aged 50-99 years). The observational studies showed no association between higher habitual milk consumption and muscle-related outcomes. The results of intervention studies using fortified milk in relation to elements of sarcopenia were also negative, with further inconclusive results from the studies using a combination of (fortified) milk and exercise. Although milk contains nutrients that may be myoprotective, current evidence does not show beneficial effects of milk on muscle health in older adults. This could be due to high habitual protein intakes (>1.0 g/kg BW/d) in study participants, differences in the type of milk (low-fat vs whole) and timing of milk consumption, length of interventions, as well as differences in the sarcopenia status of participants in trials. Adequately powered intervention studies of individuals likely to benefit are needed to test the effectiveness of a whole food approach, including milk, for healthy muscle aging., Competing Interests: The authors report no conflict of interest in this work., (© 2020 Granic et al.)

The causes of impaired skeletal muscle mass and strength during aging are well-studied in healthy populations. Less is known on pathological age-related muscle wasting and weakness termed sarcopenia, which directly impacts physical autonomy and survival. Here, we compare genome-wide transcriptional changes of sarcopenia versus age-matched controls in muscle biopsies from 119 older men from Singapore, Hertfordshire UK and Jamaica. Individuals with sarcopenia reproducibly demonstrate a prominent transcriptional signature of mitochondrial bioenergetic dysfunction in skeletal muscle, with low PGC-1α/ERRα signalling, and downregulation of oxidative phosphorylation and mitochondrial proteostasis genes. These changes translate functionally into fewer mitochondria, reduced mitochondrial respiratory complex expression and activity, and low NAD + levels through perturbed NAD + biosynthesis and salvage in sarcopenic muscle. We provide an integrated molecular profile of human sarcopenia across ethnicities, demonstrating a fundamental role of altered mitochondrial metabolism in the pathological loss of skeletal muscle mass and function in older people.

Introduction: Sarcopenia is a progressive muscle disorder characterised by decline in skeletal muscle mass, strength and function leading to adverse health outcomes, including falls, frailty, poor quality of life and death. It occurs more commonly in older people and can be accelerated by poor diet and low physical activity. Intervention studies incorporating higher dietary protein intakes or protein supplementation combined with resistance exercise (RE) have been shown to limit muscle function decline. However, less is known about the role of whole foods in reducing the risk of sarcopenia. Milk is a source of high-quality nutrients, which may be beneficial for skeletal muscle. This pilot study examines the feasibility and acceptability of milk consumption with RE to improve muscle function in community-dwelling older adults at risk of sarcopenia., Methods and Analysis: 30 older adults aged ≥65 years will be randomly allocated to three groups: 'whole milk+RE', 'skimmed milk+RE' or 'control drink+RE'. Assessments will take place in participants' homes, including screening (milk allergies, grip strength, walking speed), baseline and postintervention health and function. All participants will undertake a structured RE intervention twice a week for 6 weeks at a local gym, followed by the consumption of 500 mL of whole or skimmed milk (each ~20 g of protein) or an isocaloric control drink and another 500 mL at home. Participants' views about the study will be assessed using standardised open-ended questions. The primary outcomes include feasibility and acceptability of the intervention with recruitment, retention and intervention response rates. Analyses will include descriptive statistics, exploration of qualitative themes and intervention fidelity., Ethics and Dissemination: Outputs include pilot data to support funding applications; public involvement events; presentation at conferences and peer-reviewed publication., Trial Registration Number: ISRCTN13398279; Pre-results., Competing Interests: Competing interests: This study received ‘in-kind’ contribution from Arla., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

In recent decades, the significance of diet and dietary patterns (DPs) for skeletal muscle health has been gaining attention in ageing and nutritional research. Sarcopenia, a muscle disease characterised by low muscle strength, mass, and function is associated with an increased risk of functional decline, frailty, hospitalization, and death. The prevalence of sarcopenia increases with age and leads to high personal, social, and economic costs. Finding adequate nutritional measures to maintain muscle health, preserve function, and independence for the growing population of older adults would have important scientific and societal implications. Two main approaches have been employed to study the role of diet/DPs as a modifiable lifestyle factor in sarcopenia. An a priori or hypothesis-driven approach examines the adherence to pre-defined dietary indices such as the Mediterranean diet (MED) and Healthy Eating Index (HEI)-measures of diet quality-in relation to muscle health outcomes. A posteriori or data-driven approaches have used statistical tools-dimension reduction methods or clustering-to study DP-muscle health relationships. Both approaches recognise the importance of the whole diet and potential cumulative, synergistic, and antagonistic effects of foods and nutrients on ageing muscle. In this review, we have aimed to (i) summarise nutritional epidemiology evidence from four recent systematic reviews with updates from new primary studies about the role of DPs in muscle health, sarcopenia, and its components; (ii) hypothesise about the potential mechanisms of 'myoprotective' diets, with the MED as an example, and (iii) discuss the challenges facing nutritional epidemiology to produce the higher level evidence needed to understand the relationships between whole diets and healthy muscle ageing.

Introduction: The loss of mitochondrial function and content have been implicated in sarcopenia although they have been little studied in the very old, the group in which sarcopenia is most common. In this pilot study, our aim was to determine if mitochondrial respiratory chain function and content are preserved among healthy 85-year-olds., Methods: We recruited 19 participants (11 female) through their general practitioner and assessed their medical history, functional status and self-reported physical activity. We identified sarcopenia using grip strength, Timed Up-and-Go and bioimpedance analysis. We assessed mitochondrial respiratory chain function using phosphorous magnetic resonance spectroscopy, estimating τ 1/2 PCr, the recovery half-time of phosphocreatine in the calf muscles following a bout of aerobic exercise. We performed a biopsy of the vastus lateralis muscle and assessed mitochondrial respiratory chain content by measuring levels of subunits of complex I and IV of the respiratory chain, expressed as Z-scores relative to that in young controls., Results: Participants had a median (IQR) of 2 (1,3) long-term conditions, reported regular aerobic physical activity, and one participant (5.3%) had sarcopenia. Sixteen participants completed the magnetic resonance protocol and the mean (SD) τ 1/2 PCr of 35.6 (11.3) seconds was in keeping with preserved mitochondrial function. Seven participants underwent muscle biopsy and the mean fibre Z-scores were -0.7 (0.7) and -0.2 (0.4) for complexes I and IV, respectively, suggesting preserved content of mitochondrial respiratory chain enzymes., Conclusion: Muscle mitochondrial respiratory chain function and content are preserved in a sample of active, well-functioning 85-year-olds, among whom sarcopenia was uncommon. The results from this study will help inform future work examining the association between muscle mitochondrial deficiency and sarcopenia., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: In patients with mitochondrial DNA (mtDNA) maintenance disorders and with aging, mtDNA deletions sporadically form and clonally expand within individual muscle fibers, causing respiratory chain deficiency. This study aimed to identify the sub-cellular origin and potential mechanisms underlying this process., Methods: Serial skeletal muscle cryosections from patients with multiple mtDNA deletions were subjected to subcellular immunofluorescent, histochemical, and genetic analysis., Results: We report respiratory chain-deficient perinuclear foci containing mtDNA deletions, which show local elevations of both mitochondrial mass and mtDNA copy number. These subcellular foci of respiratory chain deficiency are associated with a local increase in mitochondrial biogenesis and unfolded protein response signaling pathways. We also find that the commonly reported segmental pattern of mitochondrial deficiency is consistent with the three-dimensional organization of the human skeletal muscle mitochondrial network., Interpretation: We propose that mtDNA deletions first exceed the biochemical threshold causing biochemical deficiency in focal regions adjacent to the myonuclei, and induce mitochondrial biogenesis before spreading across the muscle fiber. These subcellular resolution data provide new insights into the possible origin of mitochondrial respiratory chain deficiency in mitochondrial myopathy. Ann Neurol 2018;84:289-301., (© 2018 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)

Sarcopenia and osteoporosis are associated with poor health outcomes in older people. Relationships between muscle and bone have typically been reported at a functional or macroscopic level. The aims of this study were to describe the relationships between muscle morphology and bone health among participants of the Hertfordshire Sarcopenia Study (HSS). 105 older men, mean age 72.5 (SD 2.5) years, were recruited into the HSS. Whole body lean mass as well as appendicular lean mass, lumbar spine and femoral neck bone mineral content (BMC) and bone mineral density (BMD) were obtained through dual-energy X-ray absorptiometry scanning. Percutaneous biopsy of the vastus lateralis was performed successfully in 99 participants. Image analysis was used to determine the muscle morphology variables of slow-twitch (type I) and fast-twitch (type II) myofibre area, myofibre density, capillary and satellite cell (SC) density. There were strong relationships between whole and appendicular lean body mass in relation to femoral neck BMC and BMD (r ≥ 0.43, p < 0.001). Type II fibre area was associated with both femoral neck BMC (r = 0.27, p = 0.01) and BMD (r = 0.26, p = 0.01) with relationships robust to adjustment for age and height. In unadjusted analysis, SC density was associated with whole body area (r = 0.30, p = 0.011) and both BMC (r = 0.26, p = 0.031) and area (r = 0.29, p = 0.017) of the femoral neck. We have demonstrated associations between BMC and changes in muscle at a cellular level predominantly involving type II myofibres. Interventions targeted at improving muscle mass, function and quality may improve overall musculoskeletal health. Larger studies that include women are needed to explore these relationships further.

Objective: to investigate the associations between initial level and rate of change in grip strength (GS) and all-cause mortality in very old adults (≥85 years) over a 9.6-year follow-up., Methods: prospective mortality data from 845 participants in the Newcastle 85+ Study were analysed for survival in relation to GS (kg, baseline and 5-year mean change) using Cox proportional hazards models., Results: during the follow-up, 636 (75.3%) participants died. Higher baseline GS was associated with a decreased risk of mortality in all participants [hazard ratio (HR) = 0.95, 95% confidence interval (CI): 0.93-0.98, P < 0.001], men (HR = 0.97, 95% CI: 0.95-0.99, P = 0.009) and women (HR = 0.96, 95% CI: 0.94-0.99, P = 0.007) after adjustment for health, lifestyle and anthropometric factors. Overall GS slope had a downward trajectory and was determined in 602 participants: 451 experienced constant decline (negative slope) and 151 had increasing GS (positive slope) over time. Men and women with a negative slope had a 16 and 33% increased risk of mortality, respectively, with every kg/year decline in GS (P ≤ 0.005), and participants with a positive slope had a 31% decreased risk of mortality (P = 0.03) irrespective of baseline GS and key covariates., Conclusion: higher baseline GS and 5-year increase in GS were protective of mortality, whilst GS decline was associated with an increased risk of mortality in the very old over 9.6 years, especially in women. These results add to the biological and clinical importance of GS as a powerful predictor of long-term survival in late life., (© The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.)

Background: weak hand grip strength in later life is a risk factor for disability, morbidity and mortality and is central to definitions of sarcopenia and frailty. It is unclear whether rate of change in grip strength adds to level of grip strength as a risk factor for poor ageing outcomes., Methods: study participants were 292 community-dwelling men and women whose grip strength was measured during the 1994/5 (average age 67) and 2003/5 (average age 76) phases of the Hertfordshire Ageing Study, UK. Individual rate of change in grip strength was estimated using a residual change method. Mortality was followed-up to 2011 (42 men and 21 women died)., Results: average grip strengths in 2003/5 were 38.4 kg (standard deviation [SD] = 8.1) and 23.7 kg (SD = 6.6) for men and women respectively. Average annualised rates of change in grip strength (2003/5 minus 1994/5) were modest owing to a healthy-participant effect (men: -0.12 kg/y, SD = 0.71; women: 0.08 kg/y, SD = 0.54) but varied widely. Mortality risk varied according to level and rate of change in grip strength (P = 0.03); death rates per 100 person years of follow-up were 6.7 (95% CI: 4.6, 9.6) among participants who lost grip over time and had low grip in 2003/5, in contrast with 0.8 (95% CI: 0.1, 5.8) among participants whose grip changed little over time and remained high in 2003/5., Conclusions: levels of grip strength in later life should be considered in conjunction with estimates of change in grip strength identified by repeat measurement over time. Normative data for longitudinal change in grip strength are required., (© The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Introduction: Reductions in heavy manual work as a consequence of mechanisation might adversely impact muscle strength at older ages. We investigated the association between grip strength at retirement age and lifetime occupational exposure to physically demanding activities. Grip strength is an important predictor of long-term health and physical function in older people., Methods: Grip strength (maximum of three readings in each hand) was measured in men from the Hertfordshire Cohort Study at a single examination when their mean age was 65.8 (SD 2.9) years. Associations with lifetime occupational exposure (ascertained by questionnaire) to three activities (standing/walking ≥ 4 h/day; lifting ≥ 25 kg; and energetic work sufficient to induce sweating) were assessed by multivariable linear regression with adjustment for various potential confounders., Results: Complete data were available from 1418 men who had worked for at least 20 years. After adjustment for age, height and weight, those with longer exposures to walking/standing and heavy lifting had lower grip strength, but the relationship disappeared after further adjustment for confounders. Working at physical intensity sufficient to induce sweating was not significantly associated with grip strength., Conclusions: We found no evidence that physically demanding occupational activities increase hand grip strength at normal retirement age. Any advantages of regular physical occupational activity may have been obscured by unmeasured socioeconomic confounders., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Understanding the effects of muscle and fat on bone is increasingly important in the optimisation of bone health. We explored relationships between bone microarchitecture and body composition in older men and women from the Hertfordshire Cohort Study. 175 men and 167 women aged 72-81 years were studied. High resolution peripheral quantitative computed tomography (HRpQCT) images (voxel size 82 μm) were acquired from the non-dominant distal radius and tibia with a Scanco XtremeCT scanner. Standard morphological analysis was performed for assessment of macrostructure, densitometry, cortical porosity and trabecular microarchitecture. Body composition was assessed using dual energy X-ray absorptiometry (DXA) (Lunar Prodigy Advanced). Lean mass index (LMI) was calculated as lean mass divided by height squared and fat mass index (FMI) as fat mass divided by height squared. The mean (standard deviation) age in men and women was 76 (3) years. In univariate analyses, tibial cortical area (p<0.01), cortical thickness (p<0.05) and trabecular number (p<0.01) were positively associated with LMI and FMI in both men and women. After mutual adjustment, relationships between cortical area and thickness were only maintained with LMI [tibial cortical area, β (95% confidence interval (CI)): men 6.99 (3.97,10.01), women 3.59 (1.81,5.38)] whereas trabecular number and density were associated with FMI. Interactions by sex were found, including for the relationships of LMI with cortical area and FMI with trabecular area in both the radius and tibia (p<0.05). In conclusion, LMI and FMI appeared to show independent relationships with bone microarchitecture. Further studies are required to confirm the direction of causality and explore the mechanisms underlying these tissue-specific associations., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: vascular disease has been postulated to contribute to muscle dysfunction in old age. Previous studies examining the effects of cardiovascular drugs on muscle function have shown conflicting results. We therefore examined the association of angiotensin converting enzyme (ACE) inhibitor, thiazide and statin use with decline in grip strength in a well-characterised cohort., Methods: we analysed prospectively collected data from the Hertfordshire Cohort Study (HCS). For each medication, participants were divided into no baseline use/no use at follow-up, baseline use/no use at follow-up, no baseline use but use at follow-up and use at baseline and follow-up. For each group, annualised decline in grip strength (kg per year) was calculated, then adjusted for baseline age, height, weight, baseline grip strength, indices of ischaemic heart disease and hypertension. Analyses were conducted separately for males and females., Results: 639 participants were included in the analysis, mean age 65 years. 321 (50%) were male; mean follow-up time was 4.4 years. There were no differences in baseline grip between baseline users and non-users of any drug class. Adjusted grip strength change per year was similar for each group of ACE inhibitor use (P > 0.05). Similar analyses revealed no significant between-group differences for statin or thiazide use. Analysis of dropout rates by medication use revealed no evidence of selection bias., Conclusion: use of ACE inhibitors, statins or thiazides was not associated with differences in grip strength decline in healthy older people in the HCS., (© The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Sarcopenia is associated with a greater fracture risk. This relationship was originally thought to be explained by an increased risk of falls in sarcopenic individuals. However, in addition, there is growing evidence of a functional muscle-bone unit in which bone health may be directly influenced by muscle function. Because a definition of sarcopenia encompasses muscle size, strength, and physical performance, we investigated relationships for each of these with bone size, bone density, and bone strength to interrogate these hypotheses further in participants from the Hertfordshire Cohort Study. A total of 313 men and 318 women underwent baseline assessment of health and detailed anthropometric measurements. Muscle strength was measured by grip strength, and physical performance was determined by gait speed. Peripheral quantitative computed tomography (pQCT) examination of the calf and forearm was performed to assess muscle cross-sectional area (mCSA) at the 66% level and bone structure (radius 4% and 66% levels; tibia 4% and 38% levels). Muscle size was positively associated with bone size (distal radius total bone area β = 17.5 mm2 /SD [12.0, 22.9]) and strength (strength strain index (β = 23.3 mm3 /SD [18.2, 28.4]) amongst women (p < 0.001). These associations were also seen in men and were maintained after adjustment for age, height, weight-adjusted-for-height, limb-length-adjusted-for-height, social class, smoking status, alcohol consumption, calcium intake, physical activity, diabetes mellitus, and in women, years since menopause and estrogen replacement therapy. Although grip strength showed similar associations with bone size and strength in both sexes, these were substantially attenuated after similar adjustment. Consistent relationships between gait speed and bone structure were not seen. We conclude that although muscle size and grip strength are associated with bone size and strength, relationships between gait speed and bone structure and strength were not apparent in this cohort, supporting a role for the muscle-bone unit., (© 2013 American Society for Bone and Mineral Research.)

Suboptimal maternal nutrition and body composition are implicated in metabolic disease risk in adult offspring. We hypothesized that modest disruption of glucose homeostasis previously observed in young adult sheep offspring from ewes of a lower body condition score (BCS) would deteriorate with age, due to changes in skeletal muscle structure and insulin signaling mechanisms. Ewes were fed to achieve a lower (LBCS, n = 10) or higher (HBCS, n = 14) BCS before and during pregnancy. Baseline plasma glucose, glucose tolerance and basal glucose uptake into isolated muscle strips were similar in male offspring at 210 ± 4 weeks. Vastus total myofiber density (HBCS, 343 ± 15; LBCS, 294 ± 14 fibers/mm(2), P < .05) and fast myofiber density (HBCS, 226 ± 10; LBCS 194 ± 10 fibers/mm(2), P < .05), capillary to myofiber ratio (HBCS, 1.5 ± 0.1; LBCS 1.2 ± 0.1 capillary:myofiber, P < .05) were lower in LBCS offspring. Vastus protein levels of Akt1 were lower (83% ± 7% of HBCS, P < .05), and total glucose transporter 4 was increased (157% ± 6% of HBCS, P < .001) in LBCS offspring, Despite the reduction in total myofiber density in LBCS offspring, glucose tolerance was normal in mature adult life. However, such adaptations may lead to complications in metabolic control in an overabundant postnatal nutrient environment.

This review provides a framework for the development of an operational definition of sarcopenia and of the potential end points that might be adopted in clinical trials among older adults. While the clinical relevance of sarcopenia is widely recognized, there is currently no universally accepted definition of the disorder. The development of interventions to alter the natural history of sarcopenia also requires consensus on the most appropriate end points for determining outcomes of clinical importance which might be utilized in intervention studies. We review current approaches to the definition of sarcopenia and the methods used for the assessment of various aspects of physical function in older people. The potential end points of muscle mass, muscle strength, muscle power, and muscle fatigue, as well as the relationships between them, are explored with reference to the availability and practicality of the available methods for measuring these end points in clinical trials. Based on current evidence, none of the four potential outcomes in question is sufficiently comprehensive to recommend as a uniform single outcome in randomized clinical trials. We propose that sarcopenia may be optimally defined (for the purposes of clinical trial inclusion criteria as well as epidemiological studies) using a combination of measures of muscle mass and physical performance. The choice of outcome measures for clinical trials in sarcopenia is more difficult; co-primary outcomes, tailored to the specific intervention in question, may be the best way forward in this difficult but clinically important area.

Sarcopenia is the age-related loss of skeletal muscle mass and function. It is now recognised as a major clinical problem for older people and research in the area is expanding exponentially. One of the most important recent developments has been convergence in the operational definition of sarcopenia combining measures of muscle mass and strength or physical performance. This has been accompanied by considerable progress in understanding of pathogenesis from animal models of sarcopenia. Well-described risk factors include age, gender and levels of physical activity and this knowledge is now being translated into effective management strategies including resistance exercise with recent interest in the additional role of nutritional intervention. Sarcopenia is currently a major focus for drug discovery and development although there remains debate about the best primary outcome measure for trials, and various promising avenues to date have proved unsatisfactory. The concept of 'new tricks for old drugs' is, however, promising, for example, there is some evidence that the angiotensin-converting enzyme inhibitors may improve physical performance. Future directions will include a deeper understanding of the molecular and cellular mechanisms of sarcopenia and the application of a lifecourse approach to understanding aetiology as well as to informing the optimal timing of interventions.

Background: Sarcopenia is associated with disability, morbidity, and mortality. Lower birth weight is associated with reduced muscle mass and strength in older people, suggesting that developmental influences are important in sarcopenia. However, underlying mechanisms are unknown. Our objective was to determine whether low birth weight is associated with altered skeletal muscle morphology in older men., Methods: Ninety-nine men with historical records of birth weight (≤3.18 kg and ≥3.63 kg), aged 68-76 years, consented for detailed characterization of muscle, including a biopsy of the vastus lateralis. Tissue was processed for immunohistochemical studies and analyzed to determine myofibre density, area, and score., Results: Muscle fibre score (fibres kilograms per square millimeter) was significantly reduced in those with lower birth weight: 1.5 × 10(3) vs 1.7 × 10(3), p = .04 unadjusted; p = .09 adjusted for age, height, and physical activity. In addition, there was a trend for reduced myofibre density (fibres per square millimeter) in those with lower birth weight: total fibre density: 176 vs 184, type I myofibre density: 77 vs 80, and type II myofibre density: 99 vs 105. Types I and II myofibre areas (square micrometers) were larger in those with lower birth weight: type I: 4903 vs 4643 and type II: 4046 vs 3859. However, none of these differences were statistically significant., Conclusions: This is the first study showing that lower birth weight is associated with a significant decrease in muscle fibre score, suggesting that developmental influences on muscle morphology may explain the widely reported associations between lower birth weight and sarcopenia. However, the study may have been underpowered and did not include women supporting replication in larger cohorts of older men and women.

Background: Sarcopenia is defined as the loss of muscle mass and strength with age. Although a number of adult influences are recognised, there remains considerable unexplained variation in muscle mass and strength between older individuals. This has focused attention on influences operating earlier in life. Our objective for this study was to identify life course influences on muscle mass and strength in an established birth cohort and develop methodology for collection of muscle tissue suitable to investigate underlying cellular and molecular mechanisms., Methods: One hundred and five men from the Hertfordshire Cohort Study (HCS), born between 1931 and 1939 who have historical records of birth weight and weight at one year took part in the Hertfordshire Sarcopenia Study (HSS). Each participant consented for detailed characterisation of muscle mass, muscle function and aerobic capacity. In addition, a muscle biopsy of the vastus lateralis using a Weil-Blakesley conchotome was performed. Data on muscle mass, function and aerobic capacity was collected on all 105 participants. Muscle biopsy was successfully carried out in 102 participants with high rates of acceptability. No adverse incidents occurred during the study., Discussion: The novel approach of combining epidemiological and basic science characterisation of muscle in a well established birth cohort will allow the investigation of cellular and molecular mechanisms underlying life course influences on sarcopenia.

Background: A number of studies have shown strong graded positive relationships between size at birth, grip strength, and estimates of muscle mass in older people. However no studies to date have included direct measures of muscle size., Methods: We studied 313 men and 318 women born in Hertfordshire, United Kingdom between 1931 and 1939 who were still resident there and had historical records of growth in early life. Information on lifestyle was collected, and participants underwent peripheral quantitative computed tomography to directly measure forearm and calf muscle size., Results: Birth weight was positively related to forearm muscle area in the men (r = 0.24, p <.0001) and women (r = 0.17, p =.003). There were similar but weaker associations between birth weight and calf muscle area in the men (r = 0.13, p =.03) and in the women (r = 0.17, p =.004). These relationships were all attenuated by adjustment for adult size., Conclusion: We present first evidence that directly measured muscle size in older men and women is associated with size at birth. This may reflect tracking of muscle size and is important because it suggests that benefit may be gained from taking a life course approach both to understanding the etiology of sarcopenia and to developing effective interventions.

Poor prenatal nutrition is associated with a greater risk of adult glucose intolerance and insulin insensitivity in the offspring. Skeletal muscle is the primary tissue for glucose utilization, and insulin resistance in muscle is the earliest identifiable abnormality in the pre-diabetic patient. We investigated the effect of early and late gestation undernutrition on structure and markers of growth and glucose metabolism regulation in the fetal triceps brachii (TB, slow- and fast-twitch myofibres) and soleus (slow-twitch myofibres) muscles. Pregnant sheep were fed 100% nutrient requirements (C, n = 8) or a restricted diet peri-implantation (PI, n = 9; 40%, 1-31 days gestation (dGA) (term approximately 147)) or in late gestation (L, n = 6; 50%, 104-127 dGA). At 127 +/- 1 dGA we measured myofibre and capillary density in the fetal TB and soleus muscles, and mRNA levels in the TB of insulin receptor (InsR), glucose transporter-4 (GLUT-4) and type 1 insulin-like growth factor receptor (IGF-1R). Total myofibre and capillary densities were lower in the TB, but not the soleus, of PI and L fetuses. The predominant effect in the L group was on slow-twitch myofibres. In TB, InsR, GLUT-4 and IGF-1R mRNA levels were greater in L group fetuses. Our finding of reduced myofibre density is consistent with a redistribution of resources at the expense of specific peripheral tissues by early and late gestation undernutrition which may be mediated by a decrease in capillary density. The increase in key regulatory components of glucose uptake following late gestation undernutrition may constitute a short-term compensation to maintain glucose homeostasis in the face of fewer type I (insulin-sensitive) myofibres. However, together these adaptations may influence the risk of later metabolic disease and thus our findings have implications for future strategies aimed at improving maternal diet.

Recent studies have shown that people whose early growth is poor have an increased risk of sarcopenia. Sarcopenia is an important risk factor for falls, but it is not known whether poor early growth is related to falls. The authors investigated this association in the Hertfordshire Cohort Study (1998-2004), where 2,148 participants from the United Kingdom provided their history of falls. Grip strength was used as a marker of sarcopenia. Birth weight, weight at 1 year, and conditional infant growth were analyzed in relation to history of falls. The prevalence of any fall in the last year was 14.3% for men and 22.5% for women. Falls in the last year were inversely related to adult grip strength, height, and walking speed in men and women as well as to lower conditional infant growth in men (odds ratio = 1.27, 95% confidence interval: 1.04, 1.56 per standard deviation decrease in conditional infant growth; p = 0.02). This association was attenuated after adjustment for grip strength. These findings support an association between poor early growth and falls in older men that appears to be mediated partly through sarcopenia. The lack of a relation with birth weight suggests that postnatal rather than prenatal influences on muscle growth and development may be important regarding the risk of falls in later life.

Background: Sarcopenia is defined as the loss of skeletal muscle mass and strength with aging. Recent epidemiological studies have shown that men and women who grew less well in early life have lower muscle strength. Our objective was to investigate the relationship between birth weight, infant growth, and the development of sarcopenia., Methods: We studied 730 men and 673 women, of known birth weight and weight at 1 year, who were born in Hertfordshire, U.K., between 1931 and 1939. Participants completed a health questionnaire, and we measured their height, weight, and grip strength. Standard deviation scores for birth weight, and for infant growth conditional on birth weight, were analyzed in relation to grip strength before and after adjustment for adult size., Results: Grip strength was most strongly associated with birth weight in men (r = 0.19, p < .001) and women (r = 0.16, p < .001). These relationships remained significant after adjustment for adult height and weight. In contrast, the associations with infant growth were weakened after allowing for adult size. Adjustment for age, current social class, physical activity, smoking, and alcohol did not affect these results., Conclusions: Birth weight is associated with sarcopenia in men and women, independently of adult height and weight. The influence of infant growth on long-term muscle strength appears to be mediated through adult size. Sarcopenia may have its origins in early life, and identifying influences operating across the whole life course may yield considerable advances in developing effective interventions.