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Body shape expressed as the trunk-to-leg volume ratio is associated with diabetes and mortality due to the associations between higher adiposity and lower lean mass with Metabolic Syndrome (MetS) risk. Reduced appendicular muscle mass is associated with malnutrition risk and age-related frailty, and is a risk factor for poor treatment outcomes related to MetS and other clinical conditions (e.g.; cancer). These measures are traditionally assessed by dual-energy X-ray absorptiometry (DXA), which can be difficult to access in clinical settings. The Shape Up! Adults trial (SUA) demonstrated the accuracy and precision of 3-dimensional optical imaging (3DO) for body composition as compared to DXA and other criterion measures. Here we assessed whether trunk-to-leg volume estimates derived from 3DO are associated with MetS risk in a similar way as when measured by DXA. We further explored if estimations of appendicular lean mass (ALM) could be made using 3DO to further improve the accessibility of measuring this important frailty and disease risk factor. SUA recruited participants across sex, age (18–40, 40–60, >60 years), BMI (under, normal, overweight, obese), and race/ethnicity (non-Hispanic [NH] Black, NH White, Hispanic, Asian, Native Hawaiian/Pacific Islander) categories. Each participant had whole-body DXA and 3DO scans, and measures of cardiovascular health. The 3DO measures of trunk and leg volumes were calibrated to DXA to express equivalent trunk-to-leg volume ratios. We expressed each blood measure and overall MetS risk in quartile gradations of trunk-to-leg volume previously defined by National Health and Nutrition Examination Survey (NHANES). Finally, we utilized 3DO measures to estimate DXA ALM using ten-fold cross-validation of the entire dataset. Participants were 502 (273 female) adults, mean age = 46.0 ± 16.5y, BMI = 27.6 ± 7.1 kg/m2 and a mean DXA trunk-to-leg volume ratio of 1.47 ± 0.22 (females: 1.43 ± 0.23; males: 1.52 ± 0.20). After adjustments for age and sex, each standard deviation increase in trunk-to-leg volume by 3DO was associated with a 3.3 (95% odds ratio [OR] = 2.4–4.2) times greater risk of MetS, with individuals in the highest quartile of trunk-to-leg at 27.4 (95% CI: 9.0–53.1) times greater risk of MetS compared to the lowest quartile. Risks of elevated blood biomarkers as related to high 3DO trunk-to-leg volume ratios were similar to previously published comparisons using DXA trunk-to-leg volume ratios. Estimated ALM by 3DO was correlated to DXA (r 2 = 0.96, root mean square error = 1.5 kg) using ten-fold cross-validation. Using thresholds of trunk-to-leg associated with MetS developed on a sample of US-representative adults, trunk-to-leg ratio by 3DO after adjustments for offsets showed significant associations to blood parameters and MetS risk. 3DO scans provide a precise and accurate estimation of ALM across the range of body sizes included in the study sample. The development of these additional measures improves the clinical utility of 3DO for the assessment of MetS risk as well as the identification of low muscle mass associated with poor cardiometabolic and functional health. • Trunk and leg volumes by 3-dimensional optical (3DO) imaging can be calibrated to provide accurate regional volume estimates. • 3DO trunk-to-leg volume is associated with cardiometabolic blood parameters, insulin resistance, and Metabolic Syndrome. • Using a machine learning approach, 3DO can provide accurate and precise predictions of appendicular lean mass. • Development of these metrics enhances 3DO's utility for identifying cardiovascular disease and low muscle mass risk. [ABSTRACT FROM AUTHOR]

Background: Recent research has indicated a potential association between thyroid function and sarcopenia, but the specific mechanisms and a definitive causal relationship have yet to be established. Therefore, the objective of this study is to examine the potential causal connection between thyroid function and sarcopenia-related traits, including hand-grip strength, appendicular lean mass (ALM), and walking pace. Methods: The study used a bi-directional two-sample MR design, with thyroid function examined as the exposure and sarcopenia-related traits as the outcome in the first stage, and then reversed in the second stage. The genetic instruments for thyroid function were obtained from a comprehensive meta-analysis involving 271,040 participants. Data on sarcopenia-related traits based on GWASs were collected from the UK Biobank, which includes up to 461,026 European participants. The estimates for MR were calculated using the inverse-variance weighted (IVW) method, and several sensitivity analyses were performed. Results: After applying the Bonferroni correction for multiple testing, our MR analyses revealed no significant impact of thyroid function liability on sarcopenia-related traits. Similarly, our reverse MR analysis did not provide evidence supporting the influence of liability to sarcopenia-related traits on thyroid function. The results of the primary IVW MR analyses were largely in line with those obtained from our sensitivity MR analyses. Conclusion: Our research findings do not suggest a link between thyroid function and sarcopenia-related traits. The associations identified in epidemiological studies may be influenced, at least in part, by shared biological mechanisms or environmental confounders. [ABSTRACT FROM AUTHOR]

Objective: Observational studies have shown positive associations between thyroid dysfunction and risk of sarcopenia. However, the causality of this association remains unknown. This study aimed to evaluate the potential causal relationship between thyroid dysfunction and sarcopenia using Mendelian randomization (MR). Methods: This study collected pooled data from genome-wide association studies focusing on thyroid dysfunction and three sarcopenia-related features: low hand grip strength, appendicular lean mass (ALM), and walking pace, all in individuals of European ancestry. The primary analytical method used was inverse-variance weighted, with weighted median and MR-Egger serving as complementary methods to assess causal effects. Heterogeneity and pleiotropy tests were also performed, and the stability of the results was evaluated using the Leave-one-out. Results: The MR analysis indicated that hyperthyroidism could lead to a significant decrease in ALM in the extremities (OR = 1.03; 95% CI = 1.02 to 1.05; P < 0.001). The analysis also found that hypothyroidism could cause a notable reduction in grip strength (OR = 2.03; 95% CI = 1.37 to 3.01; P < 0.001) and walking pace (OR = 0.83; 95% CI = 0.77 to 0.90; P < 0.001). There was a significant association between subclinical hyperthyroidism and a reduced walking pace (OR = 1.00; 95% CI = 0.99 to 1.00; P = 0.041). Conclusion: This study provides evidence that hyperthyroidism, hypothyroidism, and subclinical hyperthyroidism can all increase the risk of sarcopenia. [ABSTRACT FROM AUTHOR]

Abstract Background Diabetes is associated with impairments in muscle mass and quality increasing the risk of sarcopenia. Thus, this study aimed to investigate the odds of sarcopenia and its associated risk factors among Qatari adults (> 18 years), while exploring the modulating effects of health and lifestyle factors. Methods Using a case–control design, data from 767 participants (481 cases with diabetes and 286 controls without diabetes) was collected from Qatar Biobank (QBB). Sociodemographic, lifestyle factors including dietary intake, anthropometric and biochemical measures were analyzed. Handgrip strength, Dual X-ray absorptiometry (DXA), and Bio-impedance were used to assess muscle strength, muscle mass and muscle quality, respectively. The risk of sarcopenia was estimated using the European consensus on definition and diagnosis of sarcopenia. Results Cases with diabetes were older (55 vs. 36 years; P

Context Although bone loss is a recognized consequence of premature ovarian insufficiency (POI), the impact on skeletal muscle health is less well-defined. Objective To compare muscle mass and function parameters between women with POI and controls. Methods Cross-sectional study from a tertiary health network and community between 2017 and 2023. Participants were women aged 20 to 40 years with POI associated with Turner syndrome (TS; n = 11) and spontaneous normal karyotype POI (s-POI; n = 7) compared with age- and body mass index (BMI)-matched controls (n = 45). Results All women with POI (mean age 28.70 ± 5.58) were using hormone therapy. Appendicular lean mass (ALM)/total fat mass and ALM/ BMI was lower in the POI group. Height-adjusted muscle mass parameters did not differ between groups. Compared with controls, women with TS and s-POI had lower muscle strength (TS 19.72 ± 4.89; s-POI 22.73 ± 5.35; controls 28.67 ± 5.65 kg; P <.001) and muscle quality (TS 11.09 ± 2.06; s-POI 10.89 ± 2.01; controls 14.10 ± 1.99 kg/kg; P <.001). Higher C-reactive protein levels, higher depression scores, and lower sex-steroid and physical activity levels were observed in women with POI (P <.05). Creatinine/cystatin C ratio, insulin-like growth factor-1, and transthyretin did not differ between groups. Conclusion Despite hormone therapy usage, women with POI exhibited compromised muscle parameters compared with age-matched controls. Potential contributory factors were identified. Further research is required to clarify pathophysiology and inform management strategies. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia (SP) and intervertebral disc degeneration (IVDD) have a higher incidence in the elderly population. Previous studies have indicated a potential association between SP and IVDD. The objective of this study is to elucidate the potential causal relationship between sarcopenia-related traits and IVDD through Two-sample Mendelian randomization (MR) analysis. Methods: We utilized a genome-wide association study conducted on the European population to collect aggregated data on sarcopenia and IVDD. Inverse variance weighting was primarily employed, supplemented by MR Egger, weighted median, simple model, and weighted model methods. Additionally, sensitivity analysis was performed to assess the robustness of the findings. Results: Appendicular lean mass is positively associated with "Other intervertebral disc disorders" (OIDD) and "Prolapsed or slipped disc" (POSD) (OIDD: p = 0.002, OR = 1.120; POSD: p < 0.001, OR = 1.003), while grip strength (GS) is positively associated with POSD (left: p = 0.004, OR = 1.008; right: p < 0.001, OR = 1.010). It is worth mentioning that walking pace has significant causal relationship with "Low back pain" (LBP), "Lower back pain or/and sciatica" (LBPOAS), "Sciatica with lumbago" (SWL) and OIDD (LBP: p < 0.001, OR = 0.204; LBPOAS: p < 0.001, OR = 0.278; SWL: p = 0.003, OR = 0.249; OIDD: p < 0.001, OR = 0.256). Conclusion: The present study revealed the causal relationship between SP-related traits and IVDD and recommended to prevent and treat sarcopenia as a means of preventing IVDD in clinic practice. [ABSTRACT FROM AUTHOR]

The relationship between appendicular lean mass (ALM) and most cardiovascular events has been established, but the direct association between ALM and atrial fibrillation (AF) remains uncertain. Herein, we identified 494 single-nucleotide polymorphisms (SNPs) strongly associated with ALM as instrumental variables (P < 5E-8) based on a genome-wide association study (GWAS) with 450,243 European participants. Then, we employed five Mendelian randomization (MR) analysis methods to investigate the causal relationship between ALM and AF. All results indicated a causal relationship between ALM and AF, among Inverse variance weighted (P = 8.44E-15, odds ratio [OR]: 1.16, 95 % confidence interval [CI]: 1.114–1.198). Furthermore, we performed a sensitivity analysis, which revealed no evidence of pleiotropy (egger_intercept = 0.000089, P = 0.965) or heterogeneity (MR Egger, Q Value = 0.980; Inverse variance weighted, Q Value = 0.927). The leave-one-out method demonstrates that individual SNPs have no driven impact on the whole causal relationship. Multivariable MR analysis indicates that, after excluding the influence of hypertension and coronary heart disease, a causal relationship between ALM and AF still exists (P = 7.74E-40, OR 95 %CI: 1.389 (1.323–1.458)). Importantly, the Radial MR framework analysis and Robust Adjusted Profile Score (RAPS) further exhibit the robustness of this causal relationship. A strong association between ALM and AF was confirmed, and high ALM is a risk factor for AF. [Display omitted] • About 494 SNPs associated with Appendicular lean mass (ALM) in 450,243 European participants. • A strong causal relationship between ALM and AF was confirmed. • High ALM is a risk factor for AF. [ABSTRACT FROM AUTHOR]

Background: Previous observational studies have linked circulating cytokines to sarcopenia, but their causal relationship remains unclear. This study employed Mendelian Randomization (MR) to investigate the causal links between circulating cytokines and sarcopenia‐related traits using genetic data. Methods: A two‐sample bidirectional MR analysis was conducted using data from individuals of European ancestry, utilizing genome‐wide association studies (GWAS) statistics. The study selected instrumental single nucleotide polymorphisms (SNPs) significantly associated with circulating cytokines and applied multiple MR methods, including inverse variance weighted (IVW), Weighted Median, MR‐Egger, Weighted Mode, Simple Mode, and MR‐PRESSO. The traits analyzed were appendicular lean mass (ALM) and grip strength. Heterogeneity, robustness, and consistency of results were assessed using Cochran's Q statistic, MR‐Egger regression, and "leave‐one‐out" sensitivity analyses. Results: The IVM‐MR analysis showed a casual association between genetically predicted circulating levels of interleukin‐16 and both ALM and grip strength (ALM: OR = 0.990, 95% CI: 0.980–1.000, p =.049; grip strength: OR = 0.971, 95% CI: 0.948–0.995, p =.020). Additionally, interferon‐gamma‐induced protein 10 (IP‐10), interleukin‐1‐beta (IL‐1β), and hepatocyte growth factor (HGF) were correlated with ALM and vascular endothelial growth factor (VEGF), interleukin‐12 (IL‐12), and interleukin‐5 (IL‐5) with grip strength. Comparable results were confirmed via the MR‐Egger, Weighted Median, Weighted Mode, and Simple Mode methods. Sensitivity analysis showed no horizontal pleiotropy to bias the causal estimates. Conclusion: The results suggest a significant causal effect of inflammatory cytokines on sarcopenia, offering new avenues for therapeutic target development. However, the study's focus on a European ancestry cohort limits its generalizability to other populations. Future research should aim to include diverse ethnic groups to validate and broaden these findings, thereby enhancing our understanding of sarcopenia's mechanisms in a global context. [ABSTRACT FROM AUTHOR]

Background: The relationship between serum lipids and sarcopenia remains unclear due to conflicting results in previous studies. Objective: To explore the associations and potential causality between serum lipids, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and total cholesterol (TC), and sarcopenia. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) were analysed using multivariable regression and restricted cubic splines (RCSs) to assess the associations between serum lipids and sarcopenia. Bidirectional Mendelian randomization (MR) was employed to investigate the causal relationships with sarcopenia-related traits such as appendicular lean mass (ALM), hand grip strength, and usual walking pace. Results: Serum HDL-C and TG levels were inversely associated with ALMBMI, with each 1-unit increase linked to a 0.13 % and 1.32 % decrease, respectively. Elevated TG, but not HDL-C, LDL-C, or TC levels, was significantly associated with an increased risk of sarcopenia (P for trend = 0.001). RCS analysis revealed a log-shaped dose-response relationship between TG and sarcopenia risk (P overall

Abstract Background Appendicular lean mass (ALM) is a good predictive biomarker for sarcopenia. And previous studies have reported the association between ALM and stroke or Alzheimer’s disease (AD), however, the causal relationship is still unclear, The purpose of this study was to evaluate whether genetically predicted ALM is causally associated with the risk of stroke and AD by performing Mendelian randomization (MR) analyses. Methods A two-sample MR study was designed. Genetic variants associated with the ALM were obtained from a large genome-wide association study (GWAS) and utilized as instrumental variables (IVs). Summary-level data for stroke and AD were generated from the corresponding GWASs. We used random-effect inverse-variance weighted (IVW) as the main method for estimating causal effects, complemented by several sensitivity analyses, including the weighted median, MR-Egger, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods. Multivariable analysis was further conducted to adjust for confounding factors, including body mass index (BMI), type 2 diabetes mellitus (T2DM), low density lipoprotein-C (LDL-C), and atrial fibrillation (AF). Results The present MR study indicated significant inverse associations of genetically predicted ALM with any ischemic stroke ([AIS], odds ratio [OR], 0.93; 95% confidence interval [CI], 0.89–0.97; P = 0.002) and AD (OR, 090; 95% CI 0.85–0.96; P = 0.001). Regarding the subtypes of AIS, genetically predicted ALM was related to the risk of large artery stroke ([LAS], OR, 0.86; 95% CI 0.77–0.95; P = 0.005) and small vessel stroke ([SVS], OR, 0.80; 95% CI 0.73–0.89; P

Abstract Background Sarcopenia is a progressive loss of muscle mass and function. Since skeletal muscle plays a critical role in metabolic homeostasis, identifying the relationship of blood metabolites with sarcopenia components would help understand the etiology of sarcopenia. Methods A two-sample Mendelian randomization study was conducted to examine the causal relationship of blood metabolites with the components of sarcopenia. Summary genetic association data for 309 known metabolites were obtained from the Twins UK cohort and KORA F4 study (7824 participants). The summary statistics for sarcopenia components [hand grip strength (HGS), walking pace (WP), and appendicular lean mass (ALM)] were obtained from the IEU Open GWAS project (461,089 participants). The inverse variance weighted method was used, and the MR-Egger, weighted median, and MR-PRESSO were used for the sensitivity analyses. Metabolic pathways analysis was further performed. Results Fifty-four metabolites associated with sarcopenia components were selected from 275 known metabolites pool. Metabolites that are causally linked to the sarcopenia components were mainly enriched in amino sugar and nucleotide sugar metabolism, galactose metabolism, fructose and mannose metabolism, carnitine synthesis, and biotin metabolism. The associations of pentadecanoate (15:0) with ALM, and 3-dehydrocarnitine and isovalerylcarnitine with HGS were significant after Bonferroni correction with a threshold of P

Background: Appendicular lean mass (ALM) is a good predictive biomarker for sarcopenia. And previous studies have reported the association between ALM and stroke or Alzheimer's disease (AD), however, the causal relationship is still unclear, The purpose of this study was to evaluate whether genetically predicted ALM is causally associated with the risk of stroke and AD by performing Mendelian randomization (MR) analyses. Methods: A two-sample MR study was designed. Genetic variants associated with the ALM were obtained from a large genome-wide association study (GWAS) and utilized as instrumental variables (IVs). Summary-level data for stroke and AD were generated from the corresponding GWASs. We used random-effect inverse-variance weighted (IVW) as the main method for estimating causal effects, complemented by several sensitivity analyses, including the weighted median, MR-Egger, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods. Multivariable analysis was further conducted to adjust for confounding factors, including body mass index (BMI), type 2 diabetes mellitus (T2DM), low density lipoprotein-C (LDL-C), and atrial fibrillation (AF). Results: The present MR study indicated significant inverse associations of genetically predicted ALM with any ischemic stroke ([AIS], odds ratio [OR], 0.93; 95% confidence interval [CI], 0.89–0.97; P = 0.002) and AD (OR, 090; 95% CI 0.85–0.96; P = 0.001). Regarding the subtypes of AIS, genetically predicted ALM was related to the risk of large artery stroke ([LAS], OR, 0.86; 95% CI 0.77–0.95; P = 0.005) and small vessel stroke ([SVS], OR, 0.80; 95% CI 0.73–0.89; P < 0.001). Regarding multivariable MR analysis, ALM retained the stable effect on AIS when adjusting for BMI, LDL-C, and AF, while a suggestive association was observed after adjusting for T2DM. And the estimated effect of ALM on LAS was significant after adjustment for BMI and AF, while a suggestive association was found after adjusting for T2DM and LDL-C. Besides, the estimated effects of ALM were still significant on SVS and AD after adjustment for BMI, T2DM, LDL-C, and AF. Conclusions: The two-sample MR analysis indicated that genetically predicted ALM was negatively related to AIS and AD. And the subgroup analysis of AIS revealed a negative causal effect of genetically predicted ALM on LAS or SVS. Future studies are required to further investigate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Aims: The causal relationship between sarcopenia‐related traits and ischemic stroke (IS) remains poorly understood. This study aimed to explore the causal impact of sarcopenia‐related traits on IS and to identify key mediators of this association. Methods: We conducted univariable, multivariable two‐sample, and two‐step Mendelian randomization (MR) analyses using genome‐wide association study (GWAS) data. This included data for appendicular lean mass (ALM), hand grip strength (HGS), and usual walking pace (UWP) from the UK Biobank, and IS data from the MEGASTROKE consortium. Additionally, 21 candidate mediators were analyzed based on their respective GWAS data sets. Results: Each 1‐SD increase in genetically proxied ALM was associated with a 7.5% reduction in the risk of IS (95% CI: 0.879–0.974), and this correlation remained after controlling for levels of physical activity and adiposity‐related indices. Two‐step MR identified that six mediators partially mediated the protective effect of higher ALM on IS, with the most significant being coronary heart disease (CHD, mediating proportion: 39.94%), followed by systolic blood pressure (36.51%), hypertension (23.87%), diastolic blood pressure (15.39%), type‐2 diabetes mellitus (T2DM, 12.71%), and low‐density lipoprotein cholesterol (7.97%). Conclusion: Our study revealed a causal protective effect of higher ALM on IS, independent of physical activity and adiposity‐related indices. Moreover, we found that higher ALM could reduce susceptibility to IS partially by lowering the risk of vascular risk factors, including CHD, hypertension, T2DM, and hyperlipidemia. In brief, we elucidated another modifiable factor for IS and implied that maintaining sufficient muscle mass may reduce the risk of such disease. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia is a progressive loss of muscle mass and function. Since skeletal muscle plays a critical role in metabolic homeostasis, identifying the relationship of blood metabolites with sarcopenia components would help understand the etiology of sarcopenia. Methods: A two-sample Mendelian randomization study was conducted to examine the causal relationship of blood metabolites with the components of sarcopenia. Summary genetic association data for 309 known metabolites were obtained from the Twins UK cohort and KORA F4 study (7824 participants). The summary statistics for sarcopenia components [hand grip strength (HGS), walking pace (WP), and appendicular lean mass (ALM)] were obtained from the IEU Open GWAS project (461,089 participants). The inverse variance weighted method was used, and the MR-Egger, weighted median, and MR-PRESSO were used for the sensitivity analyses. Metabolic pathways analysis was further performed. Results: Fifty-four metabolites associated with sarcopenia components were selected from 275 known metabolites pool. Metabolites that are causally linked to the sarcopenia components were mainly enriched in amino sugar and nucleotide sugar metabolism, galactose metabolism, fructose and mannose metabolism, carnitine synthesis, and biotin metabolism. The associations of pentadecanoate (15:0) with ALM, and 3-dehydrocarnitine and isovalerylcarnitine with HGS were significant after Bonferroni correction with a threshold of P < 1.82 × 10− 4 (0.05/275). Meanwhile, the association of hyodeoxycholate and glycine with the right HGS, and androsterone sulfate with ALM were significant in the sensitivity analyses. Conclusion: Blood metabolites from different metabolism pathways were causally related to the components of sarcopenia. These findings might benefit the understanding of the biological mechanisms of sarcopenia and targeted drugs development for muscle health. [ABSTRACT FROM AUTHOR]

Sarcopenia is among the most common musculoskeletal illnesses, yet its underlying biochemical mechanisms remain incompletely understood. In this study, we used Mendelian randomization (MR) to investigate the causal relationship between the genetically determined blood metabolites and sarcopenia, with the overall objective of identifying likely molecular pathways for sarcopenia. We used 2-sample MR to investigate the effects of blood metabolites on sarcopenia-related traits. 452 metabolites were exposure, and 3 sarcopenia-related traits as the outcomes: handgrip strength, appendicular lean mass, and walking pace. The inverse-variance weighted (IVW) causal estimates were determined. For sensitivity analysis, methods such as MR-Egger regression, the weighted median, the weighted mode, and the heterogeneity test were used. Additionally, for complementation, we performed replication, meta-analysis, and metabolic pathway analyses. Candidate biomarkers were defined by meeting one of the following criteria: (1) significant metabolites are defined as p IVW <  p Bonferroni [1.11 × 10−4 (.05/452)]; (2) strong metabolites are defined as 4 MR methods p  < .05; and (3) suggestive metabolites are defined as passing sensitivity analysis. Three metabolites (creatine, 1-arachidonoylglycerophosphocholine, and pentadecanoate [15:0]) with significant causality, 3 metabolites (glycine, 1-arachidonoylglycerophosphocholine, and epiandrosterone sulfate) with strong causality, and 25 metabolites (including leucylleucin, pyruvic acid, etc.) with suggestive causality were associated with sarcopenia-related traits. After further replication analyses and meta-analysis, these metabolites maintained substantial effects on sarcopenia-related traits. We additionally identified 14 important sarcopenia-related trait metabolic pathways. By combining metabolomics with genomics, these candidate metabolites and metabolic pathways identified in our study may provide new clues regarding the mechanisms underlying sarcopenia. [ABSTRACT FROM AUTHOR]

ObjectiveTo explore the causal relationships between 91 circulating inflammatory cytokines and sarcopenia-related traits (low hand grip strength, appendicular lean mass, and usual walking pace) by Mendelian randomized analysis.MethodsIndependent genetic variations of inflammatory cytokines and sarcopenia-related traits were selected as instrumental variables from publicly available genome-wide association studies (GWAS). The MR analysis was primarily conducted using the inverse variance-weighted (IVW) method. Sensitivity analyses included Steiger filtering and MR PRESSO, with additional assessments for heterogeneity and pleiotropy.ResultsThe IVW method indicated a causal relationship between Vascular Endothelial Growth Factor A (VEGF-A) and low hand grip strength (OR = 1.05654, 95% CI: 1.02453 to 1.08956, P = 0.00046). Additionally, Tumor Necrosis Factor-beta (TNF-β) was found to have a causal relationship with appendicular lean mass (ALM) (β = 0.04255, 95% CI: 0.02838 to 0.05672, P = 3.96E-09). There was no evidence suggesting a significant causal relationship between inflammatory cytokines and usual walking pace.ConclusionOur research substantiated the causal association between inflammatory cytokines, such as VEGF-A and TNF-β, and sarcopenia. This finding may provide new avenues for future clinical treatments.

Objective: Investigating the causal relationship between Lachnospiraceae and Appendicular lean mass (ALM) and identifying and quantifying the role of Aminopeptidase O Protein (AOPEP) as a potential mediator. Methods: The summary statistics data of gut microbiota composition from the largest available genome-wide association study (GWAS) meta-analysis conducted by the MiBioGen Consortium (n = 13,266). Appendicular lean mass data were obtained from the UK-Biobank (n = 450,243). We conducted bidirectional two-sample Mendelian randomization (MR) analysis using summary-level data from GWAS to investigate the causal relationship between Lachnospiraceae and ALM. Additionally, we employed a drug-targeted MR approach to assess the causal relationship between AOPEP and ALM. Finally, a two-step MR was employed to quantitatively estimate the proportion of the effect of Lachnospiraceae on ALM that is mediated by AOPEP. Cochran's Q statistic was used to quantify heterogeneity among instrumental variable estimates. Results: In the MR analysis, it was found that an increase in genetically predicted Lachnospiraceae [OR = 1.031, 95% CI (1.011-1.051), P = 0.002] is associated with an increase in ALM. There is no strong evidence to suggest that genetically predicted ALM has an impact on Lachnospiraceae genus [OR = 1.437, 95% CI (0.785-2.269), P = 0.239]. The proportion of genetically predicted Lachnospiraceae mediated by AOPEP was 34.2% [95% CI (1.3%-67.1%)]. Conclusion: Our research reveals that increasing Lachnospiraceae abundance in the gut can directly enhance limb muscle mass and concurrently suppress AOPEP, consequently mitigating limb muscle loss. This supports the potential therapeuticmodulation of gutmicrobiota for sarcopenia. Interventions such as drug treatments or microbiota transplantation, aimed at elevating Lachnospiraceae abundance and AOPEP inhibition, synergistically improve sarcopenia in the elderly, thereby enhancing the overall quality of life for older individuals. [ABSTRACT FROM AUTHOR]

There is an association between body composition and lung function, assessed by spirometry, but the effects of body compartments on static lung volumes and its changes during lung growth remain to be explored. We aimed to investigate the association of appendicular lean mass, reflecting skeletal muscle mass, and fat mass on forced and static lung function measures in childhood and adolescence. In total, 1489 children and adolescents (6–18 years) of the observational, longitudinal (first and second visit within 4 years), general population-based LEAD study have been investigated. The association of appendicular lean mass and fat mass indices (ALMI and FMI; assessed by dual-energy X-ray absorptiometry) on lung function by spirometry (FEV 1 , FVC) and body plethysmography (TLC, RV, FRC) was investigated cross-sectionally. Longitudinal associations between lung function and body compartment changes between the two visits were analyzed. The ALMI is positively associated with FEV 1 , FVC, and TLC. Contrary, FMI is inversely associated with lung function measures including FRC and RV. During the phase of lung growth, higher gain in muscle mass is associated with higher increases of FVC and TLC. This study demonstrates the different effects of muscle and fat mass on forced expiratory and static lung volumes. Achieving and maintaining muscle mass in childhood and adolescence might become an important preventive strategy for lung health in adulthood. [ABSTRACT FROM AUTHOR]

The relationship between body weight and bone mass in the elderly remains unclear, and whether obesity is a protective factor is still a matter of debate. For this reason, the aim of this study is to assess the association between body mass index (BMI) and bone mineral content adjusted by body weight, expressed as a percentage (w-BMC%), and to test the validity of the obesity paradox in this context. A cohort of 1404 older adults was categorized according to the World Health Organization's BMI cut-off points and completed a total and segmental body composition measurement by means of a dual X-ray absorptiometry scan. Individuals with obesity displayed a lower mean w-BMC% (3.06 ± 0.44%; 2.60 ± 0.37%) compared to those who were normal-weight (3.95 ± 0.54%; 3.38 ± 0.48%) and overweight (3.06 ± 0.44%; 3.04 ± 0.37%) in both genders. Linear regression analysis also showed a negative association between BMI and w-BMC% in males (β = −0.09; p < 0.001) and females (β = −0.06; p < 0.001). Finally, among individuals with obesity, and after adjusting for age, the linear regression models revealed a significant decrease of 0.75% and 0.28% in w-BMC% for every one-unit increase in the trunk fat/appendicular lean mass ratio in both males (β = −0.749; p < 0.0001) and females (β = −0.281; p < 0.001). In conclusion, we suggest a new paradigm regarding the impact of obesity on bone mass, in which the former does not appear to be a protective factor of the latter, especially in individuals with central obesity and low muscle mass. [ABSTRACT FROM AUTHOR]

BackgroundThe causal association of sarcopenia with the incidence risk of hepatocellular carcinoma (HCC) in the European population, and the potential mediating role of C-reactive protein (CRP), remains unclear. This study employed a bidirectional two-sample, two-step Mendelian randomization (MR) analysis to investigate the causality and identify the mediator.MethodsSummary statistics for HCC, CRP, and sarcopenia-related traits, including appendicular lean mass (ALM), hand grip strength (HGS), and walking pace (WP), were acquired from publicly available databases. We conducted bidirectional MR and Steiger tests of directionality to check the presence of reverse causality. Additionally, a two-step MR analysis was used to assess the mediating effect of CRP in the causality between sarcopenia and HCC. Tests for heterogeneity and horizontal pleiotropy were performed.ResultsAs ALM increases, the risk of HCC occurrence decreases [odds ratio (OR), 95% confidence interval (CI): 0.703, 0.524–0.943; P = 0.019]. And, genetically predicted low-HGS (OR, 95%CI: 2.287, 1.013–5.164; P = 0.047) was associated with an increased incidence risk of HCC, with no reverse causality. However, we found no evidence supporting a causality between WP and HCC. CRP was identified as the mediator of the causal effect of ALM and low-HGS on HCC, with corresponding mediating effects of 9.1% and 7.4%.ConclusionsThis MR study effectively demonstrates that lower ALM and low-HGS are linked to an elevated risk of HCC within the European population, and the causality was not bidirectional. Furthermore, CRP serves as a mediator in the associations. These findings may help mitigate HCC risk among individuals with sarcopenia.

Qing Su,1 Chen Jin,2 Yi Yang,1 Jingxian Wang,1 Juejin Wang,1 Hao Zeng,1 Yaqing Chen,1 Junxi Zhou,1 Yi Wang1 1Department of Epidemiology and Biostatistics, School of Public Health and Management, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Yi Wang, Department of Epidemiology and Biostatistics, School of Public Health and Management, Wenzhou Medical University, Chashan High Education Zone, Wenzhou, Zhejiang, 325035, People’s Republic of China, Tel +86-577-8669-9358, Email wang.yi@wmu.edu.cnPurpose: Observational studies have reported that autoimmune diseases are closely related to sarcopenia, but the causalities of autoimmune diseases with sarcopenia have not been established. We conducted this Mendelian randomization (MR) study to reveal the causal associations of overall autoimmune disease and five common autoimmune diseases with sarcopenia-related traits.Methods: The publicly available summary-level data of autoimmune diseases and three sarcopenia-related traits were used for analysis. The causal effects of autoimmune diseases on sarcopenia-related traits were first identified in discovery samples using the inverse-variance-weighted method as the primary method, and the robustness of results was examined by additional sensitivity analyses. Replication MR analyses were then conducted using replication samples of five autoimmune diseases. Finally, the possibility of reverse causation was assessed by reverse MR analyses.Results: In both the discovery and replication samples, we identified potential causal effects of rheumatoid arthritis (RA) on appendicular lean mass (ALM) and low grip strength (OR = 0.979, 95% CI: 0.964– 0.995 for ALM; OR = 1.042, 95% CI: 1.013– 1.072 for low grip strength), but not on walking pace. We also found that inflammatory bowel disease (IBD) and type 1 diabetes (T1D) were only causally negatively associated with ALM in the discovery stage (OR = 0.986, 95% CI: 0.974– 0.999 for IBD; OR = 0.987, 95% CI: 0.975– 0.999 for T1D), whereas systemic lupus erythematosus, multiple sclerosis, and overall autoimmune disease were not associated with any of the three sarcopenia-related traits. Additionally, reverse MR analysis only found an association between walking pace and overall autoimmune disease, but this association did not remain in the weighted-median method.Conclusion: This study demonstrates that RA is causally associated with low grip strength and reduced ALM, and that IBD and T1D may be causally negatively related to ALM.Keywords: Mendelian randomization, autoimmune disease, sarcopenia, rheumatoid arthritis, grip strength, appendicular lean mass

Background: Observational studies have shown an association between reduced renal function and the risk of sarcopenia. However, the causal relationship and the underlying biological mechanisms remain uncertain. Using a Mendelian randomization (MR) framework, we investigated the causal role of 27 hypothetical risk mediators, including metabolites, hormones, inflammation, and stress traits, on the risk of sarcopenia. Methods: Instrumental variables (IVs) to proxy renal function were identified by selecting single nucleotide polymorphisms (SNPs) reliably associated with creatinine and cystatin C-based glomerular filtration rate (GFR) in CKDGen summary data. IVs for putative risk traits and sarcopenia traits were constructed from relevant genome-wide association studies (GWAS). MR estimated effects were obtained using an inverse-variance weighted effects model, and various sensitivity analyses were performed. The mediating role of hypothetical risk factors in the relationship between GFR and sarcopenia was assessed through multivariate MR. Results: Genetically predicted reduced GFRcrea was associated with higher odds of appendicular lean mass (ALM) (odds ratio (OR): 0.64, 95% confidence interval (CI) 0.37 to 0.68) and grip strength (OR: 0.67; 95% CI 0.58 to 0.78). Likewise, GFRcys highlighted a causal relationship with ALM (OR: 0.52; 95% CI 0.42 to 0.65) and grip strength (OR: 0.66; 95% CI 0.59 to 0.74). Both estimated GFR (eGFR) were negatively associated with IGF-1, IL-16, 25(OH)D, triglycerides (range of effect size per standard deviation: -0.81 to -0.30), and positively correlated with HDL cholesterol (0.62, 0.31). There was a positive correlation between IGF-1, fasting insulin and ALM as well as grip strength (OR range: 1.04–1.67) and a negative correlation between serum CRP and ALM (OR: 0.95) as well as grip strength (OR: 0.98). Additionally, genetically predicted IL-1β (OR: 0.95) and total cholesterol (OR: 0.96) were negatively associated with ALM. We found evidence that IGF-1 mediates the relationship between eGFR and risk for muscle mass and strength. Conclusions: This MR study provides insight into the potential causal mechanisms between renal function and the risk of sarcopenia and proposes IGF-1 as a potential target for the prevention of renal sarcopenia.

BackgroundSarcopenia, a progressive loss of skeletal muscle mass and strength, needs to initially prevent in the twenties. Meanwhile, there is a lack of research on the effects of fat consumption on skeletal muscle mass and strength in adults aged 20–59. We aimed to assess associations between dietary fat intake and skeletal muscle mass, as measured by appendicular lean mass adjusted for body mass index (ALMBMI), and muscle strength, as represented by handgrip strength adjusted for body mass index (GSMAXBMI), among adults aged 20–59.MethodsDietary fat intake per kilogram of actual body weight was assessed using two 24h recalls, while ALM and GSMAX were measured using DXA and a handgrip dynamometer, respectively. A weighted multiple linear regression model was employed to analyze the association between dietary fat intake and skeletal muscle mass, utilizing data from the National Health and Nutrition Examination Survey spanning from 2011 to 2014. To assess the non-linear relationship and saturation value between dietary fat intake and skeletal muscle mass, a smooth curve fitting approach and a saturation effect analysis model were utilized.ResultsThe study comprised a total of 5356 subjects. After adjusting for confounding factors, there was a positive association observed between dietary fat intake and ALMBMI as well as GSMAXBMI. The relationship between dietary fat intake and ALMBMI showed an inverted U-shaped curve, as did the association with GSMAXBMI. Turning points were observed at 1.88 g/kg/d for total fat intake and ALMBMI, as well as at 1.64 g/kg/d for total fat intake and GSMAXBMI. Furthermore, turning points were still evident when stratifying by gender, age, protein intake, and physical activity. The turning points were lower in individuals with low protein intake(

Background: Both benign prostatic hyperplasia (BPH) and sarcopenic obesity (SO) are common conditions among older adult/adults males. The prevalent lifestyle associated with SO is a significant risk factor for the development of BPH. Therefore, we investigated the causal relationship between SO factors and BPH. Method: The instrumental variables for SO factors were selected using the inverse variance-weighted method, which served as the primary approach for Mendelian randomization analysis to assess the causal effect based on summary data derived from genome-wide association studies of BPH. Result: The increase in BMR (OR = 1.248; 95% CI = (1.087, 1.432); P = 0.002) and ALM (OR = 1.126; 95% CI = (1.032, 1.228); P = 0.008) was found to be associated with an elevated risk of BPH. However, no genetic causality between fat-free mass distribution, muscle mass distribution, and BPH was observed. Conclusion: Our findings indicate that a genetic causal association between BMR, ALM and BPH. BMR and ALM are risk factors for BPH. The decrease in BMR and ALM signified the onset and progression of SO, thus SO is a protective factor for BPH. [ABSTRACT FROM AUTHOR]

Background: The two geriatric diseases, sarcopenia and cardiovascular disease (CVD), often coexist, yet the causal relationship is unclear. However, few studies focus on the effect of muscle mass on CVD. This comprehensive study is dedicated to unearthing the potential connection between sarcopenia-related traits and CVD at the genetic level. Method: A two-sample bi-directional Mendelian randomization (MR) study was conducted. In the first stage, we performed MR analysis regarding coronary heart disease (CHD), stroke, and myocardial infarction (MI) as exposure factors to reveal their effect on appendicular lean mass (ALM) and hand grip strength. In the second stage, we reverse the position of exposures and outcomes. The inverse variance weighted (IVW) method was used as the primary approach to reveal the potential causation between the exposure and outcome. Results: The results of the IVW method revealed a negative causal effect of ALM on CHD (OR = 0.848, 95% CI = 0.804 to 0.894, p = 8.200E-10), stroke (OR = 0.931, 95% CI = 0.890 to 0.975, p = 2.220E-03), and MI (OR = 0.810, 95% CI = 0.694 to 0.901, p = 1.266E-13). Additionally, the left-hand grip strength is a significant protective factor for CHD (OR = 0.737, 95% CI = 0.601 to 0.904, p = 3.353E-03) and MI (OR = 0.631, 95% CI = 0.515 to 0.765, p = 2.575E-06), but is not causally linked to the stroke (OR = 0.971, 95% CI =0.829 to 1.139, p = 0.720). Meanwhile, the same conclusion about the effect of right-hand grip strength on CHD (OR = 0.681, 95% CI = 0.558 to 0.832, p = 1.702E-05), MI (OR = 0.634, 95% CI = 0.518 to 0.776, p = 9.069E-06), and stroke (OR = 1.041, 95% CI = 0.896 to 1.209, p = 0.604) was obtained. However, no significant causal effect of CVD (CHD, stroke, MI) on sarcopenia-related traits (ALM, handgrip strength) was found. Conclusion: There is a unidirectional causal relationship between sarcopenia and CVD. The loss of muscle mass and strength has a significant causal role in promoting the occurrence and development of CVD, providing a reference for the prevention and treatment of comorbidities in older people. [ABSTRACT FROM AUTHOR]

Metabolites' connection to sarcopenia through inflammation and mitochondrial dysfunction is presumed, but their impact remains unclear due to limitations in conventional observational studies caused by confounding bias and reverse causation. We conducted a Mendelian randomization (MR) analysis to elucidate the association of serum metabolites with sarcopenia and its related traits, i.e., appendicular lean mass and grip strength. Genetic instruments to proxy the serum metabolites were extracted from the most comprehensive genome-wide association study on the topic published so far. The corresponding summary statistics for the associations of genetic instruments with outcomes were calculated from the UK Biobank (n = 324,976 participants). The primary analyses were assessed by an inverse-variance weighted (IVW) method. The weighted median and MR-PRESSO methods were used as sensitive analyses. Fourteen genetically predicted serum metabolites were associated with the risk of sarcopenia (PIVW < 0.05). Two metabolites showed the overlapped association with sarcopenia and its related traits, which were isovalerylcarnitine (sarcopenia: odds ratio [OR] = 4.00, 95% confidence interval [CI] = 1.11~14.52, PIVW = 0.034; appendicular lean mass: β = −0.45 kg, 95% CI = −0.81~−0.09, PIVW = 0.015; grip strength: β = −1.51 kg, 95% CI = −2.31~−0.71, PIVW = 2.19 × 10−4) and docosapentaenoate (sarcopenia: OR = 0.16, 95% CI = 0.03~0.83, PIVW = 0.029; appendicular lean mass: β = −0.45 kg, 95% CI = 0.08~0.81, PIVW = 0.016). Twenty-seven metabolites were suggestive associated with appendicular lean mass or grip strength. This MR study provided evidence for the potential effects of metabolites on sarcopenia. [ABSTRACT FROM AUTHOR]

Background and purpose: Observational studies have shown that sarcopenia and diabetic nephropathy (DN), are closely related; however, the causal relationship is unclear. This study aims to address this issue using a bidirectional Mendelian randomization (MR) study. Methodology: We data from genome-wide association studies including appendicular lean mass (n = 244,730), grip strength (right: n = 461,089, left: n = 461026), walking speed (n = 459,915), and DN (3283 cases and 181,704 controls) to conduct a bidirectional MR study. First, we conducted a Forward MR analysis to evaluate the causality of sarcopenia on the risk of DN fromthe genetic perspective with appendicular lean mass, grip strength, and walking speed as exposure and DN as the outcome. Then, DN as the exposure, we performed a ReverseMR analysis to determine whether DN impacted the appendicular lean mass, grip strength, and walking speed of the appendices. Finally, a series of sensitivity studies, such as heterogeneity tests, pleiotropy evaluations, and Leave-one-out analyses, were conducted to assess the MR analysis's accuracy further. Results: According to a forward MR analysis, a genetically predicted decrease in appendicular lean mass is associated with an increased risk of developing DN risk (inverse variance weighting[IVW]: odd ratio [OR] = 0.863, 95% confidence interval [CI] 0.767-0.971; P = 0.014). According to reverse MR results, grip strength decreased as DN progressed (IVW: right b = 0.003, 95% CI: - 0.021 to - 0.009, P = 5.116e-06; left b = 0.003, 95% CI: - 0.024 to - 0.012, P = 7.035e-09). However, the results of the other MR analyses were not statistically different. Conclusion: Notably, our findings suggest that the causal relationship between sarcopenia and DN cannot be generalized. According to analysis of the individual characteristic factors of sarcopenia, reducing in appendicular lean mass increases the risk of developing DN and DN is linked to reduced grip strength. But overall, there is no causal relationship between sarcopenia and DN, because the diagnosis of sarcopenia cannot be determined by one of these factors alone. [ABSTRACT FROM AUTHOR]

Background This narrative review describes foundational and emerging evidence of how dietary protein intakes may influence muscle-related attributes of older adults. Methods PubMed was used to identify pertinent research. Results Among medically stable older adults, protein intakes below the recommended dietary allowance (RDA) (0.8 g/kg body weight [BW]/d) exacerbate age-related reductions in muscle size, quality, and function. Dietary patterns with total protein intakes at or moderately above the RDA, including one or preferably more meals containing sufficient dietary protein to maximize protein anabolism, promote muscle size and function. Some observational studies suggest protein intakes from 1.0 to 1.6 g/kg BW/d may promote greater muscle strength and function more so than muscle size. Experimental findings from randomized controlled feeding trials indicate protein intakes greater than the RDA (averaging ~1.3 g/kg BW/d) do not influence indices of lean body mass or muscle and physical functions with non-stressed conditions, but positively influence changes in lean body mass with purposeful catabolic (energy restriction) or anabolic (resistance exercise training) stressors. Among older adults with diagnosed medical conditions or acute illness, specialized protein or amino acid supplements that stimulate muscle protein synthesis and improve protein nutritional status may attenuate the loss of muscle mass and function and improve survival of malnourished patients. Observational studies favor animal versus plant protein sources for sarcopenia-related parameters. Conclusions Quantity, quality, and patterning of dietary protein consumed by older adults with varied metabolic states, and hormonal and health status influence the nutritional needs and therapeutic use of protein to support muscle size and function. [ABSTRACT FROM AUTHOR]

Abstract Background Early detection and management of sarcopenia is of clinical importance. We aimed to develop a chest X‐ray‐based deep learning model to predict presence of sarcopenia. Methods Data of participants who visited osteoporosis clinic at Severance Hospital, Seoul, South Korea, between January 2020 and June 2021 were used as derivation cohort as split to train, validation and test set (65:15:20). A community‐based older adults cohort (KURE) was used as external test set. Sarcopenia was defined based on Asian Working Group 2019 guideline. A deep learning model was trained to predict appendicular lean mass (ALM), handgrip strength (HGS) and chair rise test performance from chest X‐ray images; then the machine learning model (SARC‐CXR score) was built using the age, sex, body mass index and chest X‐ray predicted muscle parameters along with estimation uncertainty values. Results Mean age of the derivation cohort (n = 926; women n = 700, 76%; sarcopenia n = 141, 15%) and the external test (n = 149; women n = 95, 64%; sarcopenia n = 18, 12%) cohort was 61.4 and 71.6 years, respectively. In the internal test set (a hold‐out set, n = 189, from the derivation cohort) and the external test set (n = 149), the concordance correlation coefficient for ALM prediction was 0.80 and 0.76, with an average difference of 0.18 ± 2.71 and 0.21 ± 2.28, respectively. Gradient‐weight class activation mapping for deep neural network models to predict ALM and HGS commonly showed highly weight pixel values at bilateral lung fields and part of the cardiac contour. SARC‐CXR score showed good discriminatory performance for sarcopenia in both internal test set [area under the receiver‐operating characteristics curve (AUROC) 0.813, area under the precision‐recall curve (AUPRC) 0.380, sensitivity 0.844, specificity 0.739, F1‐score 0.540] and external test set (AUROC 0.780, AUPRC 0.440, sensitivity 0.611, specificity 0.855, F1‐score 0.458). Among SARC‐CXR model features, predicted low ALM from chest X‐ray was the most important predictor of sarcopenia based on SHapley Additive exPlanations values. Higher estimation uncertainty of HGS contributed to elevate the predicted risk of sarcopenia. In internal test set, SARC‐CXR score showed better discriminatory performance than SARC‐F score (AUROC 0.813 vs. 0.691, P = 0.029). Conclusions Chest X‐ray‐based deep leaning model improved detection of sarcopenia, which merits further investigation.

Background: Previous studies have reported an association between sarcopenia and type 2 diabetes mellitus (T2DM), but causation was prone to confounding factors. A more robust research approach is urgently required to investigate the causal relationship between sarcopenia and T2DM. Methods: The bi-directional two-sample MR study was carried out in two stages: Sarcopenia-related traits were investigated as exposure while T2DM was investigated as an outcome in the first step, whereas the second step was reversed. The GWAS summary data for hand-grip strength (n = 256,523), appendicular lean mass (ALM, n = 450,243), and walking pace (n = 459,915) were obtained from the UK Biobank. T2DM data were obtained from one of the biggest case-control studies on diabetes (DIAGRAM; n = 180,834 cases and 492,191 controls), which was published in 2022. The inverse-variance weighted (IVW) approach was used to obtain MR estimates, and various sensitivity analysis was also performed. Results: Low hand-grip strength had a potential causal relationship with an increased incidence of T2DM (OR = 1.109; 95% CI, 1.008-1.222; p = 0.0350). T2DM risk was reduced by increasing ALM and walking pace: A 1 kg/m² increase in ALM decreased the risk of T2DM by 10.2% (OR = 0.898; 95% CI, 0.830-0.952; p < 0.001). A1 m/s increase in walking pace decreased the risk of T2DM by 90.0% (OR = 0.100; 95% CI, 0.053-0.186; p < 0.001). The relationship was bidirectional, with T2DM as a causative factor of sarcopenia-related traits (p < 0.05) except for ALM (β = 0.018; 95% CI, -0.008 to -0.044; p = 0.168). Conclusions: Hand-grip strength and T2DM had a potential bidirectional causal relationship, as did walking pace and T2DM. We suggest that sarcopenia and T2DM may mutually have a significant causal effect on each other. [ABSTRACT FROM AUTHOR]

BackgroundThe association of BMI with COPD, and sarcopenia in COPD have been both confirmed by several studies, but research on the relationship and causality of body lean mass and the risk of chronic obstructive pulmonary disease (COPD) remains to be discovered. The purpose of this study was to explore the association between lean mass and COPD risk as well as to further examine the causal relationship in the findings.MethodsThree thousand four hundred fifty-nine participants from NHANES 2013–2018 were included in the epidemiological cross-sectional study to assess the association between relative lean mass and COPD by restricted spline analysis (RCS) and weighted multiple logistic regression. Furthermore, to verify the causality between lean mass and COPD, a two-sample Mendelian randomization (MR) with inverse variance weighting (IVW) method was used to analyze GWAS data from European ancestry. Genetic data from the United Kindom Biobank for appendicular lean mass (450,243 cases) and lung function (FEV1/FVC) (400,102 cases) together with the FinnGen platform for COPD (6,915 cases and 186,723 controls) were used for MR.ResultsWeighted multiple logistic regression showed a significant correlation between relative appendicular lean mass and COPD after adjusting for confounders (OR = 0.985, 95% CI: 0.975–0.995). Compared to the lower mass (155.3–254.7) g/kg, the high mass (317.0–408.5) g/kg of appendicular lean apparently decreases the risk of COPD (OR = 0.214, 95% CI: 0.060–0.767). Besides, in the analysis of MR, there was a forward causality between appendicular lean mass and COPD (IVW: OR = 0.803; 95%CI: 0.680–0.949; p = 0.01), with a weak trend of causality to lung function.ConclusionOur study not only found an inverse association between appendicular lean mass and COPD but also supported a unidirectional causality. This provided possible evidence for further identification of people at risk for COPD and prevention of COPD based on limb muscle exercise and nutritional supplementation to maintain skeletal muscle mass.

Abstract Introduction Rheumatoid arthritis (RA) is an autoimmune disease, characterized by chronic and systemic inflammation. Besides, it is known that RA patients may present several comorbidities, such as sarcopenia, a condition where patients present both muscle mass and muscle quality impairment. RA treatment is mostly pharmacological and consists in controlling systemic inflammation and disease activity. Despite that, the effect of pharmacological treatment on sarcopenia is not well characterized. Objective To summarize the effects of disease-modifying anti-rheumatic drugs (DMARDs) on skeletal muscle tissue in rheumatoid arthritis (RA) patients. Methods A systematic review of randomized clinical trials and observational studies was conducted using MEDLINE, Embase, Cochrane Library, and Web of Science. We selected studies with rheumatoid arthritis patients treated with disease-modifying anti-rheumatic drugs (DMARDs) that analyzed muscle mass parameters such as lean mass and appendicular lean mass. Methodological quality was assessed using the Newcastle-Ottawa Quality Assessment Scale. Standardized mean difference (SMD) and 95% confidence intervals (CI) were set. A meta-analysis of observational studies was performed using the R software, and we considered significant statistics when p < 0.05. Results Nine studies were included in this systematic review. In the meta-analysis, DMARD treatment had no positive difference (p = 0.60) in lean mass. In the same way, in the appendicular lean mass parameter, our results showed that DMARDs did not have changes between baseline and post-treatment analysis (p = 0.93). Conclusion There is no evidence of a significant effect of DMARD therapy, either synthetic or biological, on muscle mass. However, this association should be investigated with more studies.

The relationship between serum lipids and sarcopenia remains unclear due to conflicting results in previous studies. To explore the associations and potential causality between serum lipids, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and total cholesterol (TC), and sarcopenia. Data from the National Health and Nutrition Examination Survey (NHANES) were analysed using multivariable regression and restricted cubic splines (RCSs) to assess the associations between serum lipids and sarcopenia. Bidirectional Mendelian randomization (MR) was employed to investigate the causal relationships with sarcopenia-related traits such as appendicular lean mass (ALM), hand grip strength, and usual walking pace. Serum HDL-C and TG levels were inversely associated with ALMBMI, with each 1-unit increase linked to a 0.13 % and 1.32 % decrease, respectively. Elevated TG, but not HDL-C, LDL-C, or TC levels, was significantly associated with an increased risk of sarcopenia (P for trend = 0.001). RCS analysis revealed a log-shaped dose-response relationship between TG and sarcopenia risk (P overall <0.001, P non-linear <0.001), with a cutoff value of 92.75 mg/dL. Genetically predicted HDL-C, LDL-C, and TG were associated with ALM. Conversely, ALM showed an inverse causal relationship with all four serum lipids. Additionally, genetically predicted usual walking pace influenced HDL-C and TG levels (P < 0.001). The study reveals a nonlinear association between TG levels and sarcopenia risk, and a bidirectional association between lipid profiles and muscle mass, underscoring the need for further research to elucidate these mechanisms. • Serum triglyceride (TG) levels exceeding 92.75 mg/dL (1.047 mmol/L) are associated with an increased risk of sarcopenia. • Genetically determined levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) exhibit a bidirectional causal relationship with appendicular lean mass (ALM). • The genetically predicted usual walking pace was found to influence levels of HDL-C and TG. [ABSTRACT FROM AUTHOR]

To investigate relationship between depression and handgrip strength (HGS) and appendicular lean mass (ALM) in Young and middle-aged adults.Cross-sectional study.Data from participants aged 20-59 from the 2011-2014 National Health and Nutrition Examination Survey.In a study of 4927 middle-aged Americans, 2564 (52.30%) were men and 2363 (47.7%) were women, with an average age of 38.57 ± 11.72. Among this group, 716 individuals (14.53%) experienced mild depression, while 385 individuals (7.81%) suffered from moderate to severe depression.Data of HGS and ALM were collected by handgrip test, and whole-body dual-energy X-ray absorptiometry scans. Depression was assessed using the Patient Health Questionnaire-9. Linear and logistic regression, restricted cubic spline regression analyses and subgroup analysis were conducted to evaluate the association.Following multivariate logistic regression analysis, the study showed that a 1-point increase in the depression score was associated with a 4% increase in the probability of reduced grip strength for both males (95% CI: 1.01-1.07) and females (95% CI: 1.01-1.06). Additionally, for males, there was a 5% increase in the likelihood of decreased muscle mass (95% CI: 1.01-1.09), whereas the decline in muscle mass for females did not exhibit statistical significance. Subgroup analysis indicated that the inverse relationship between depression and grip strength, along with the negative association between depression and muscle mass among males, remained consistent in the 40-59 age range.This research revealed an inverse relationship between depression and grip strength in middle-aged and young individuals, and a negative association between depression and ALM was only noted in males. Early intervention could be beneficial from age 40. [ABSTRACT FROM AUTHOR]

Background and Purpose: Prior observational studies have suggested a strong correlation between sarcopenia and stroke, but the causal link between them remains uncertain. This study aims to investigate the associations between genetically predicted sarcopenia-related traits and stroke using a two-step Mendelian randomization (MR) approach., Methods: Genome-wide association study (GWAS) summary data for sarcopenia-related traits were acquired from the UK Biobank. Genetic associations for ischemic stroke (IS) and its subtypes were selected from the MEGASTROKE consortium comprising European ancestry participants. GWAS summary data for cerebral hemorrhage were obtained from the FinnGen consortium, including intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). MR estimates were calculated using the inverse-variance weighted (IVW) method. The robustness of results was assessed for heterogeneity and pleiotropy of individual single nucleotide polymorphisms (SNPs)., Results: Higher appendicular lean mass (ALM) exhibited a potential causal association with a reduced incidence of large artery atherosclerosis (LAA) (odds ratio [OR] = 0.81, 95% confidence interval [CI]:0.71-0.93; P = 0.003) and small vessel disease (SVD) (OR = 0.83, 95% CI:0.74-0.94; P = 0.002). The associations of ALM with IS and ICH were compromised after adjusting for body fat and physical activity with multivariable MR. Two-step MR mediation analysis explored 33 candidate mediators, among which hypertension and SBP accounted for more than 10% of the mediation proportion in the relationship between ALM and stroke and its subtypes., Conclusion: Our research findings indicate that lower ALM is associated with a increased risk of stroke . It is necessary to explore the specific protective mechanisms of higher ALM for preventing stroke occurrence., Competing Interests: Declaration of competing interest The authors declared that there were no potential conflicts of interest regarding this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Recent research has indicated a potential association between thyroid function and sarcopenia, but the specific mechanisms and a definitive causal relationship have yet to be established. Therefore, the objective of this study is to examine the potential causal connection between thyroid function and sarcopenia-related traits, including hand-grip strength, appendicular lean mass (ALM), and walking pace., Methods: The study used a bi-directional two-sample MR design, with thyroid function examined as the exposure and sarcopenia-related traits as the outcome in the first stage, and then reversed in the second stage. The genetic instruments for thyroid function were obtained from a comprehensive meta-analysis involving 271,040 participants. Data on sarcopenia-related traits based on GWASs were collected from the UK Biobank, which includes up to 461,026 European participants. The estimates for MR were calculated using the inverse-variance weighted (IVW) method, and several sensitivity analyses were performed., Results: After applying the Bonferroni correction for multiple testing, our MR analyses revealed no significant impact of thyroid function liability on sarcopenia-related traits. Similarly, our reverse MR analysis did not provide evidence supporting the influence of liability to sarcopenia-related traits on thyroid function. The results of the primary IVW MR analyses were largely in line with those obtained from our sensitivity MR analyses., Conclusion: Our research findings do not suggest a link between thyroid function and sarcopenia-related traits. The associations identified in epidemiological studies may be influenced, at least in part, by shared biological mechanisms or environmental confounders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Li and Xu.)

Objective: Observational studies have shown positive associations between thyroid dysfunction and risk of sarcopenia. However, the causality of this association remains unknown. This study aimed to evaluate the potential causal relationship between thyroid dysfunction and sarcopenia using Mendelian randomization (MR)., Methods: This study collected pooled data from genome-wide association studies focusing on thyroid dysfunction and three sarcopenia-related features: low hand grip strength, appendicular lean mass (ALM), and walking pace, all in individuals of European ancestry. The primary analytical method used was inverse-variance weighted, with weighted median and MR-Egger serving as complementary methods to assess causal effects. Heterogeneity and pleiotropy tests were also performed, and the stability of the results was evaluated using the Leave-one-out., Results: The MR analysis indicated that hyperthyroidism could lead to a significant decrease in ALM in the extremities (OR = 1.03; 95% CI = 1.02 to 1.05; P < 0.001). The analysis also found that hypothyroidism could cause a notable reduction in grip strength (OR = 2.03; 95% CI = 1.37 to 3.01; P < 0.001) and walking pace (OR = 0.83; 95% CI = 0.77 to 0.90; P < 0.001). There was a significant association between subclinical hyperthyroidism and a reduced walking pace (OR = 1.00; 95% CI = 0.99 to 1.00; P = 0.041)., Conclusion: This study provides evidence that hyperthyroidism, hypothyroidism, and subclinical hyperthyroidism can all increase the risk of sarcopenia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wei, Hou, Hei and Wang.)

Background: Currently, it is unclear whether there is a causal association between genetically predicted plasma homocysteine (Hcy) levels and the risk of sarcopenia. We performed a Mendelian randomization (MR) study to assess the association between circulating Hcy levels and the components [grip strength, walking pace, and appendicular lean mass (ALM)] of sarcopenia.Methods: Independent single nucleotide polymorphisms (SNPs) significantly associated with plasma Hcy levels served as instrumental variables. Summary-level data regarding the components of sarcopenia. Were obtained from the UK Biobank. Inverse variance weighted (IVW) as the primary method was used for Mendelian randomization (MR) analysis. We also use four models, weighted median, MR-Egger regression, Maximum likelihood, and Penalised weighted median, as supplementary methods to IVW. The MR-Egger intercept test, Cochran’s Q test, and “leave-one-out” sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of the causal association between Hcy levels and the components of sarcopenia.Results: The IVW-MR analysis suggested significant negative associations of increased plasma Hcy levels with grip strength (right: effect = −0.036, SE = 0.032, p = 5.53E-4; left: effect = −0.045, SE = 0.010, p = 1.45E-5), walking pace (effect = −0.038, SE = 0.011, p = 3.18E-4), and ALM (effect = −0.058, 0.013, p = 1.03E-5). However, there were no significant associations of decreased plasma Hcy levels with grip strength (right: effect = 0.005, SE = 0.021, p = 0.82; left: effect = −0.006, SE = 0.014, p = 0.64), walking pace (effect = 0.01, 0.020, p = 0.61), or ALM (effect = -0.034, SE = 0.018, p = 0.06).The accuracy and robustness of these findings were confirmed by sensitivity tests.Conclusion: Increased circulating Hcy levels were associated with lower grip strength, slower walking pace, and decreased ALM.

• MR shows T regulatory cells and CD127 marker linked to sarcopenia traits like ALM. • MCSF and HGF cytokines positively associated with appendicular lean mass in sarcopenia. • No direct causal effect of sarcopenia on immune markers, indicating complex interplays. • Identifies specific immune and cytokines markers' contributions to sarcopenia, aiding targeted therapies. Recent studies have suggested a possible link between sarcopenia, immune dysregulation, and chronic inflammation, although the specific immune components implicated remain unclear. This investigation employs Mendelian Randomization (MR) to explore the reciprocal relationship between immune cells, inflammatory markers, and sarcopenia. We performed two-sample and multivariate MR analyses using publicly accessible genome-wide association studies (GWAS) summary statistics. Our analyses included 731 immune cells, 41 inflammatory cytokines, and sarcopenia related traits (appendicular lean mass [ALM], low hand-grip strength [LHS], and walking pace [WP]), with additional sensitivity analyses conducted to confirm the findings. After false discovery rate (FDR) correction, significant associations were found between ten immune traits and ALM, with the CD127 marker in the Treg panel showing consistent positive correlation across four sites. In contrast, NKT%lymphocyte negatively correlated with WP (OR = 0.99, P = 0.023). In terms of inflammatory cytokines, macrophage colony-stimulating factor (MCSF) (OR = 1.03, P = 0.024) and hepatocyte growth factor (HGF) (OR = 1.03, P = 0.002) demonstrated positive associations with ALM, while interleukin-16 (IL-16) (OR = 0.99, P = 0.006) was inversely related. The reverse Mendelian randomization analysis found no direct causal links between sarcopenia traits and immune or inflammatory markers. Sensitivity analyses underscored the findings' resilience to pleiotropy, and adjusting for inter-trait dynamics weakened these relationships in the multivariable MR analysis. Our study reveals causal associations between specific immune phenotypes, inflammatory cytokines, and sarcopenia, providing insight into the development of sarcopenia and potential treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Low bone density (BMD) and fractures commonly affect women with premature ovarian insufficiency (POI). However, bone microarchitecture and body composition data are lacking. Objective: To assess and characterise musculoskeletal phenotype and effects of oestrogen replacement therapy (ERT) in women with POI. Method: Cross-sectional and longitudinal studies of 60 normal karyotype women with POI, aged 20-40 years, from 2005-2018. Dual x-ray absorptiometry (DXA)-derived spinal (LS) and femoral neck (FN) BMD, trabecular bone score (TBS), appendicular lean mass (ALM), total fat mass (TFM), and fracture prevalence were compared with 60 age-, and BMI-matched population-based controls. Longitudinal changes in bone and body composition variables and ERT effects were analysed using linear mixed models over a median duration of 6 years. Results: Women with POI were subdivided into spontaneous (s)-POI (n=25) and iatrogenic (i)-POI (n=35). Median(range) age of POI diagnosis was 34 (10-40) years with baseline DXA performed at median 1(0-13) year post-diagnosis. ERT was used by 82% women (similar for both POI groups). FN-BMD were lowest in s-POI (p<0.002). Low TBS was more common in s-POI [(44%), p=0.03], versus other groups. LS-BMD and ALM were lower in both s-POI and i-POI groups than controls (p<0.05). Fracture prevalence was not significantly different: 20% (s-POI), 17% (i-POI), and 8% (controls) (p=0.26). Longitudinal analysis of 23 POI women showed regular ERT was associated with ALM increment of 127.05 g/year (p<0.001) and protected against bone loss. However, ERT interruption was associated with annual reductions in FN BMD and TBS of 0.020g/cm2 and 0.0070 (p<0.05), respectively. Conclusion: Deficits in BMD, trabecular microarchitecture, and lean mass were present in women with POI. However, regular ERT protected against declines in bone variables, with an increase in ALM. Assessment of skeletal and muscle health, and advocating ERT adherence, is essential in POI to optimise musculoskeletal outcomes. [ABSTRACT FROM AUTHOR]

Whole-body dual X-ray absorptiometry (DXA) accurately measures lean mass but is not routinely used in clinical practice. Hip and spine DXA are used in the diagnosis of osteoporosis, and with the common co-occurrence of sarcopenia with osteoporosis, regional DXA scans provide an opportunity for assessment of lean mass. The aim of this study is to develop predictive equations for the estimation of whole-body lean mass (WBLM), appendicular lean mass (ALM) and whole-body fat mass (WBFM) from regional DXA scans. A total of 2427 participants (ages 20–96 year; 57.7% men) from the Geelong Osteoporosis Study who underwent both regional and whole-body DXA were included in the analysis. Using forward stepwise multivariable linear regression, percentage fat (spine%fat, hip%fat) values from lumbar spine and femoral neck DXA were used in combination with clinical data to develop and validate equations for the estimation of WBLM, WBFM and ALM. Mean age was 53.5 year (± 19.2), weight 78.2 kg (± 15.4), height 169.6 cm (± 9.4), WBLM 50.4 kg (± 11.1), ALM 22.8 kg (± 5.4) and WBFM 24.3 kg (± 10.4). Spine%fat (r = 0.21) and hip%fat (r = − 0.34) were correlated with whole-body lean mass (p < 0.001). Final predictive equations included age, sex, weight, height, spine%fat, and hip%fat and possessed high predictive value (Adj R2 0.91–0.94, RMSE 1.60–2.84 kg). K-fold cross-validation methods produced median root mean square error (RMSE) ranging from 1.59 to 2.81 kg for the three models. Regional DXA scans of the spine and hip can be used to estimate whole-body and appendicular lean mass, to assist in the identification of low muscle mass. [ABSTRACT FROM AUTHOR]

BackgroundLow bone density (BMD) and fractures commonly affect women with premature ovarian insufficiency (POI). However, bone microarchitecture and body composition data are lacking.ObjectiveTo assess and characterise musculoskeletal phenotype and effects of oestrogen replacement therapy (ERT) in women with POI.MethodCross-sectional and longitudinal studies of 60 normal karyotype women with POI, aged 20-40 years, from 2005-2018. Dual x-ray absorptiometry (DXA)-derived spinal (LS) and femoral neck (FN) BMD, trabecular bone score (TBS), appendicular lean mass (ALM), total fat mass (TFM), and fracture prevalence were compared with 60 age-, and BMI-matched population-based controls. Longitudinal changes in bone and body composition variables and ERT effects were analysed using linear mixed models over a median duration of 6 years.ResultsWomen with POI were subdivided into spontaneous (s)-POI (n=25) and iatrogenic (i)-POI (n=35). Median(range) age of POI diagnosis was 34 (10-40) years with baseline DXA performed at median 1(0-13) year post-diagnosis. ERT was used by 82% women (similar for both POI groups). FN-BMD were lowest in s-POI (p

Background: Sarcopenia, a progressive loss of skeletal muscle mass and strength, can begin in the 4th decade of life. Protein intake predicts skeletal muscle mass and strength among older adults, but knowledge of similar associations among middle-aged adults is lacking.Objectives: We aimed to assess associations between protein intake and skeletal muscle mass, characterized by appendicular lean mass adjusted for BMI [in kg/m2 (ALMBMI)], and muscle strength, represented by handgrip strength adjusted for BMI (GSMAXBMI), among middle-aged adults.Methods: We analyzed cross-sectional data from 1209 men and 1208 women aged 40-59 y in the 2011-2014 NHANES. Protein intake per kilogram actual body weight (BW), assessed by two 24-h recalls, was examined as continuous and categorical parameters [low (Results: Among middle-aged adults, 15.6% of men and 13.4% of women had low lean mass and 3.5% of men and 2.3% of women exhibited weakness. Protein intakes per kilogram BW were positively associated with ALMBMI and GSMAXBMI among men and women after adjustment for age, race/Hispanic origin, physical activity, and self-rated health. Compared with the moderate protein group, the high protein group had a higher GSMAXBMI and the low protein group had a lower GSMAXBMI among men and women. The low protein group had a lower ALMBMI (women) and had a higher OR for low lean mass (men) compared with the moderate protein group.Conclusions: Higher protein intakes were associated with greater ALMBMI and GSMAXBMI in this representative sample of US middle-aged adults. Our findings highlight the need for further research on dietary protein as a potential modifying factor of sarcopenia risk in middle age. [ABSTRACT FROM AUTHOR]

Mediterranean dietary patterns may exert favourable effects on various health conditions. This study aimed to determine associations of adherence to Mediterranean diet as well as its components, with circulating cytokine levels, musculoskeletal health and incident falls in community-dwelling older men. Seven hundred ninety-four (794) community-dwelling men with mean age 81.1 ± 4.5 years, who participated in the five-year follow-up of the Concord Health and Ageing in Men Project (CHAMP) were included in the cross-sectional analysis, and 616 attended follow-up three years later. Adherence to Mediterranean diet was assessed using MEDI-LITE (literature-derived Mediterranean diet) score which was obtained using a validated diet history questionnaire. Twenty-four evaluable circulating cytokines were analyzed using Bio-Plex Pro Human Cytokine 27-plex Assay kit. Appendicular lean mass (ALM) and bone mineral density (BMD) were measured using dual-energy x-ray absorptiometry (DXA). Three-year changes in gait speed and hand grip strength were assessed by walking a 6-m course and using a dynamometer respectively and analyzed using linear mixed-effects models. Incident falls over three years were determined through telephone interviews every four months. Multivariable linear regression was utilized to determine the cross-sectional associations between MEDI-LITE scores and circulating cytokines, bone mineral density, ALM, and ALM BMI. Linear mixed-effects models were performed to estimate associations between MEDI-LITE scores and three-year change in hand grip strength and gait speed while negative binomial regression was applied to estimate associations between MEDI-LITE scores and three-year incident falls as well as associations between each MEDI-LITE component and three-year incident falls. Adjustments for multiple comparisons were performed using Benjamini-Hochberg adjustment for multiple testing. A higher MEDI-LITE score, indicating greater adherence to Mediterranean diet, was associated with higher appendicular lean mass adjusted for body mass index (ALM BMI) (β: 0.004 kg; 95% CI: 0.000, 0.008), and lower incident falls rates (IRR: 0.94; 95% CI: 0.89, 0.99). Higher consumption of monounsaturated fatty acids (IRR: 0.76; 95% CI: 0.59, 0.98) and monounsaturated fatty acids to saturated fatty acids ratio (IRR: 0.72; 95% CI: 0.57, 0.90) were associated with 24%, and 28% lower falls risk in older men respectively. MEDI-LITE scores were not associated with BMD or physical function parameters. Adherence to a Mediterranean diet is associated with higher ALM BMI , and fewer falls in community-dwelling older men. Monounsaturated and saturated fatty acids were the most important contributors to the association between Mediterranean diet and falls risk. [ABSTRACT FROM AUTHOR]

Objective: To explore the causal relationships between 91 circulating inflammatory cytokines and sarcopenia-related traits (low hand grip strength, appendicular lean mass, and usual walking pace) by Mendelian randomized analysis., Methods: Independent genetic variations of inflammatory cytokines and sarcopenia-related traits were selected as instrumental variables from publicly available genome-wide association studies (GWAS). The MR analysis was primarily conducted using the inverse variance-weighted (IVW) method. Sensitivity analyses included Steiger filtering and MR PRESSO, with additional assessments for heterogeneity and pleiotropy., Results: The IVW method indicated a causal relationship between Vascular Endothelial Growth Factor A (VEGF-A) and low hand grip strength (OR = 1.05654, 95% CI: 1.02453 to 1.08956, P = 0.00046). Additionally, Tumor Necrosis Factor-beta (TNF-β) was found to have a causal relationship with appendicular lean mass (ALM) (β = 0.04255, 95% CI: 0.02838 to 0.05672, P = 3.96E-09). There was no evidence suggesting a significant causal relationship between inflammatory cytokines and usual walking pace., Conclusion: Our research substantiated the causal association between inflammatory cytokines, such as VEGF-A and TNF-β, and sarcopenia. This finding may provide new avenues for future clinical treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sun, Liu, Yin, Li and Liu.)

Background Adequate total and meal-specific protein intake is considered an important prerequisite to preserve appendicular lean mass (ALM) in older adults and to prevent sarcopenia. Objectives We analyzed the meal-specific protein intake across the main meals between participants with normal vs. low ALM to BMI ratio (ALMBMI). Methods 782 participants [59.6% men; median 69 (IQR: 65, 71) y] of the Berlin Aging Study II have been included in this analysis. ALM was assessed by dual X-ray absorptiometry. Low lean mass was defined as ALMBMI using recommended sex-specific cut-offs. A 5-day nutritional protocol was used to assess total and meal-specific protein intake. Results Median total protein intake was 0.89 (IQR: 0.74, 1.05) g/kg/d body weight (BW) in participants with low ALMBMI and 1.02 (IQR: 0.86, 1.21) g/kg BW in participants with normal ALMBMI (P  < 0.001). Daily protein intake at breakfast was similar in both groups [0.23 (95% CI: 0.20, 0.26) vs. 0.24 (95% CI: 0.23, 0.26) g/kg BW; P  = 0.245]. Subjects with low ALMBMI reported a lower protein intake at lunch and dinner compared with those with normal ALMBMI [0.29 (95% CI: 0.27, 0.32) vs. 0.35 (95% CI: 0.34, 0.36) g/kg BW; P  = 0.001 and 0.32 (95% CI: 0.30, 0.35) vs. 0.36 (95% CI: 0.35, 0.37) g/kg BW; P  = 0.027, respectively]. In a stepwise regression model, a higher total protein intake was positively associated with ALMBMI [ß = 0.10 (95% CI: 0.07, 0.13) P  < 0.001]. The protein intake at dinner was positively associated with ALMBMI [ß = 0.14 (95% CI: 0.08, 0.19) P  < 0.001] irrespective of protein intake at breakfast and lunch. This association disappeared after additional adjustment for total protein intake. Conclusion Our data highlight an association of total protein intake and ALMBMI in older adults. Although current data support an association of high ALMBMI with protein intake at dinner in particular, this was not independent from total protein intake and the findings do not allow a conclusion on causality. [ABSTRACT FROM AUTHOR]

Abstract Background Half of cancer cases occur in patients aged 70 and above. Majority of older patients are eligible for chemotherapy but evidence for treating this population is sparse and severe toxicities affect more than half of them. Determining prognostic biomarkers able to predict poor chemotherapy tolerance remains one of the major issues in geriatric oncology. Ageing is associated with body composition changes (increase of fat mass and loss of lean mass) independently of weight-loss. Previous studies suggest that body composition parameters (particularly muscle mass) may predict poor chemotherapy tolerance. However, studies specifically including older adults on this subject remain sparse and the majority of them study body composition based on computed tomography (CT) scanner (axial L3 section) muscle mass estimation. This method is to date not validated in elderly cancer patients. Methods This trial (Fraction) will evaluate the discriminative ability of appendicular lean mass measured by dual-energy X-ray absorptiometry (DXA) to predict severe toxicity incidence in older cancer-patients treated with first-line chemotherapy. DXA is considered the gold standard in body composition assessment in older adults. Patient’s aged ≥70 diagnosed with solid neoplasms or lymphomas at a locally advanced or metastatic stage treated for first-line chemotherapy were recruited. Patients completed a pre-chemotherapy assessment that recorded socio-demographics, tumor/treatment variables, laboratory test results, geriatric assessment variables (function, comorbidity, cognition, social support and nutritional status), oncological risk scores and body composition with DXA. Appendicular lean mass was standardized using evidence based international criteria. Participants underwent short follow-up geriatric assessments within the first 3 months, 6 months and a year after inclusion. Grade 3 to 5 chemotherapy-related toxicities, as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) were assessed at each chemotherapy cycle. Discussion The finding that body composition is associated with poor tolerance of chemotherapy could lead to consider these parameters as well as improve current decision-making algorithms when treating older adults. Trial registration ClinicalTrials.gov Identifier: NCT02806154 registered on October 2016.