ORCID Profile
0009-0008-5853-8096
Current Organisation
University of Southampton
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Publisher: Elsevier BV
Date: 03-2023
Publisher: Wiley
Date: 05-01-2023
DOI: 10.1002/JCSM.13160
Abstract: The 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) and the Sarcopenia Definitions and Outcomes Consortium (SDOC) have recently proposed sarcopenia definitions. However, comparisons of the performance of these approaches in terms of thresholds employed, concordance in in iduals and prediction of important health‐related outcomes such as death are limited. We addressed this in a large multinational assembly of cohort studies that included information on lean mass, muscle strength, physical performance and health outcomes. White men from the Health Aging and Body Composition (Health ABC) Study, Osteoporotic Fractures in Men (MrOS) Study cohorts (Sweden, USA), the Hertfordshire Cohort Study (HCS) and the Sarcopenia and Physical impairment with advancing Age (SarcoPhAge) Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA muscle strength by grip dynamometry and usual gait speed over courses of 2.4–6 m. Deaths were recorded and verified. Definitions of sarcopenia were as follows: EWGSOP2 (grip strength kg and ALM index .0 kg/m 2 ), SDOC (grip strength .5 kg and gait speed .8 m/s) and Modified SDOC (grip strength .5 kg and gait speed .0 m/s). Cohen's kappa statistic was used to assess agreement between original definitions (EWGSOP2 and SDOC). Presence versus absence of sarcopenia according to each definition in relation to mortality risk was examined using Cox regression with adjustment for age and weight estimates were combined across cohorts using random‐effects meta‐analysis. Mean (SD) age of participants ( n = 9170) was 74.3 (4.9) years 5929 participants died during a mean (SD) follow‐up of 12.1 (5.5) years. The proportion with sarcopenia according to each definition was EWGSOP2 (1.1%), SDOC (1.7%) and Modified SDOC (5.3%). Agreement was weak between EWGSOP2 and SDOC (κ = 0.17). Pooled hazard ratios (95% CI) for mortality for presence versus absence of each definition were EWGSOP2 [1.76 (1.42, 2.18), I 2 : 0.0%] SDOC [2.75 (2.28, 3.31), I 2 : 0.0%] and Modified SDOC [1.93 (1.54, 2.41), I 2 : 58.3%]. There was low prevalence and poor agreement among recent sarcopenia definitions in community‐dwelling cohorts of older white men. All indices of sarcopenia were associated with mortality. The strong relationship between sarcopenia and mortality, regardless of the definition, illustrates that identification of appropriate management and lifecourse intervention strategies for this condition is of paramount importance.
Publisher: Springer Science and Business Media LLC
Date: 29-03-2023
DOI: 10.1038/S41586-023-05772-8
Abstract: Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being 1–6 . Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was .1 kg m –2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have lified.
Publisher: Springer Science and Business Media LLC
Date: 20-12-2019
DOI: 10.1038/S41467-019-13694-1
Abstract: 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. In iduals 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.
Publisher: Wiley
Date: 15-06-2021
DOI: 10.1002/RCO2.44
Abstract: Despite increasing knowledge of the pathogenesis of muscle ageing, the molecular mechanisms are poorly understood. Based on an expression analysis of muscle biopsies from older Caucasian men, we undertook an in‐depth analysis of the expression of the long non‐coding RNA, H19 , to identify molecular mechanisms that may contribute to the loss of muscle mass with age. We carried out transcriptome analysis of vastus lateralis muscle biopsies from 40 healthy Caucasian men aged 68–76 years from the Hertfordshire Sarcopenia Study (HSS) with respect to appendicular lean mass adjusted for height (ALMi). Validation and replication was carried out using qRT‐PCR in 130 independent male and female participants aged 73–83 years recruited into an extension of the HSS (HSSe). DNA methylation was assessed using pyrosequencing. Lower ALMi was associated with higher muscle H19 expression ( r 2 = 0.177, P 0.001). The microRNAs, miR‐675‐5p/3p encoded by exon 1 of H19 , were positively correlated with H19 expression (Pearson r = 0.192 and 0.182, respectively, P 0.03), and miR‐675‐5p expression negatively associated with ALMi ( r 2 = 0.629, P = 0.005). The methylation of CpGs within the H19 imprinting control region (ICR) were negatively correlated with H19 expression (Pearson r = −0.211 to −0.245, P ≤ 0.05). Moreover, RNA and protein levels of SMAD1 and 5 , targets of miR‐675‐3p , were negatively associated with miR‐675‐3p ( r 2 = 0.792 and 0.760, respectively) and miR‐675‐5p ( r 2 = 0.584 and 0.723, respectively) expression, and SMAD1 and 5 RNA levels positively associated with greater type II fibre size ( r 2 = 0.184 and 0.246, respectively, P 0.05). Increased expression profiles of H19/miR‐675‐5p/3p and lower expression of the anabolic SMAD1/5 effectors of bone morphogenetic protein (BMP) signalling are associated with low muscle mass in older in iduals.
Publisher: Elsevier BV
Date: 06-2021
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Leo Westbury.