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Introduction Older people have been reported to be at higher risk of COVID-19 mortality. This study explored the factors mediating this association and whether older age was associated with increased mortality risk in the absence of other risk factors. Methods In UK Biobank, a population cohort study, baseline data were linked to COVID-19 deaths. Poisson regression was used to study the association between current age and COVID-19 mortality. Results Among eligible participants, 438 (0.09%) died of COVID-19. Current age was associated exponentially with COVID-19 mortality. Overall, participants aged ≥75 years were at 13-fold (95% CI 9.13–17.85) mortality risk compared with those <65 years. Low forced expiratory volume in 1 second, high systolic blood pressure, low handgrip strength, and multiple long-term conditions were significant mediators, and collectively explained 39.3% of their excess risk. The associations between these risk factors and COVID-19 mortality were stronger among older participants. Participants aged ≥75 without additional risk factors were at 4-fold risk (95% CI 1.57–9.96, P = 0.004) compared with all participants aged <65 years. Conclusions Higher COVID-19 mortality among older adults was partially explained by other risk factors. ‘Healthy’ older adults were at much lower risk. Nonetheless, older age was an independent risk factor for COVID-19 mortality.

SummaryVARP is a Rab32/38 effector that also binds to the endosomal/lysosomal R-SNARE VAMP7. VARP binding regulates VAMP7 participation in SNARE complex formation and can therefore influence VAMP7-mediated membrane fusion events. Mutant versions of VARP that cannot bind Rab32:GTP, designed on the basis of the VARP ankyrin repeat/Rab32:GTP complex structure described here, unexpectedly retain endosomal localization, showing that VARP recruitment is not dependent on Rab32 binding. We show that recruitment of VARP to the endosomal membrane is mediated by its direct interaction with VPS29, a subunit of the retromer complex, which is involved in trafficking from endosomes to the TGN and the cell surface. Transport of GLUT1 from endosomes to the cell surface requires VARP, VPS29, and VAMP7 and depends on the direct interaction between VPS29 and VARP. Finally, we propose that endocytic cycling of VAMP7 depends on its interaction with VARP and, consequently, also on retromer.

Background Sarcopenia is defined as the loss of muscle mass and strength. Despite the seriousness of this disease, a single diagnostic criterion has not yet been established. Few studies have reported the prevalence of sarcopenia globally, and there is a high level of heterogeneity between studies, stemmed from the diagnostic criteria of sarcopenia and the target population. The aims of this systematic review and meta-analysis were (i) to identify and summarize the diagnostic criteria used to define sarcopenia and severe sarcopenia and (ii) to estimate the global and region-specific prevalence of sarcopenia and severe sarcopenia by sociodemographic factors. Methods Embase, MEDLINE, and Web of Science Core Collections were searched using relevant MeSH terms. The inclusion criteria were cross-sectional or cohort studies in individuals aged ≥18 years, published in English, and with muscle mass measured using dual-energy x-ray absorptiometry, bioelectrical impedance, or computed tomography (CT) scan. For the meta-analysis, studies were stratified by diagnostic criteria (classifications), cut-off points, and instruments to assess muscle mass. If at least three studies reported the same classification, cut-off points, and instrument to measure muscle mass, they were considered suitable for meta-analysis. Following this approach, 6 classifications and 23 subgroups were created. Overall pooled estimates with inverse-variance weights obtained from a random-effects model were estimated using the metaprop command in Stata. Results Out of 19 320 studies, 263 were eligible for the narrative synthesis and 151 for meta-analysis (total n = 692 056, mean age: 68.5 years). Using different classifications and cut-off points, the prevalence of sarcopenia varied between 10% and 27% in the studies included for meta-analysis. The highest and lowest prevalence were observed in Oceania and Europe using the European Working Group on Sarcopenia in Older People (EWGSOP) and EWGSOP2, respectively. The prevalence ranged from 8% to 36% in individuals <60 years and from 10% to 27% in ≥60 years. Men had a higher prevalence of sarcopenia using the EWGSOP2 (11% vs. 2%) while it was higher in women using the International Working Group on Sarcopenia (17% vs. 12%). Finally, the prevalence of severe sarcopenia ranged from 2% to 9%. Conclusions The prevalence of sarcopenia and severe sarcopenia varied considerably according to the classification and cut-off point used. Considering the lack of a single diagnostic for sarcopenia, future studies should adhere to current guidelines, which would facilitate the comparison of results between studies and populations across the globe.

Background: Resistance exercise increases muscle mass and function in older adults, but responses are attenuated compared with younger people. Data suggest that long-chain n–3 polyunsaturated fatty acids (PUFAs) may enhance adaptations to resistance exercise in older women. To our knowledge, this possibility has not been investigated in men.Objective: We sought to determine the effects of long-chain n–3 PUFA supplementation on resistance exercise training–induced increases in muscle mass and function and whether these effects differ between older men and women.Design: Fifty men and women [men: n = 27, mean ± SD age: 70.6 ± 4.5 y, mean ± SD body mass index (BMI; in kg/m2): 25.6 ± 4.2; women: n = 23, mean ± SD age: 70.7 ± 3.3 y, mean ± SD BMI: 25.3 ± 4.7] were randomly assigned to either long-chain n–3 PUFA (n = 23; 3 g fish oil/d) or placebo (n = 27; 3 g safflower oil/d) and participated in lower-limb resistance exercise training twice weekly for 18 wk. Muscle size, strength, and quality (strength per unit muscle area), functional abilities, and circulating metabolic and inflammatory markers were measured before and after the intervention.Results: Maximal isometric torque increased after exercise training to a greater (P < 0.05) extent in the long-chain n–3 PUFA group than in the placebo group in women, with no differences (P > 0.05) between groups in men. In both sexes, the effect of exercise training on maximal isokinetic torque at 30, 90, and 240° s−1, 4-m walk time, chair-rise time, muscle anatomic cross-sectional area, and muscle fat did not differ (P > 0.05) between groups. There was a greater (P < 0.05) increase in muscle quality in women after exercise training in the long-chain n–3 PUFA group than in the placebo group, with no such differences in men (P > 0.05). Long-chain n–3 PUFAs resulted in a greater decrease (P < 0.05) than the placebo in plasma triglyceride concentrations in both sexes, with no differences (P > 0.05) in glucose, insulin, or inflammatory markers.Conclusion: Long-chain n–3 PUFA supplementation augments increases in muscle function and quality in older women but not in older men after resistance exercise training. This trial was registered at clinicaltrials.gov as NCT02843009.

Background: Recent systematic reviews have suggested that pedometers may be effective motivational tools to promote walking. However, studies tend to be of a relatively short duration, with small clinical based samples. Further research is required to demonstrate their effectiveness in adequately powered, community based studies.

Chronic kidney disease is common in the general population and associated with excess cardiovascular disease (CVD), but kidney function does not feature in current CVD risk prediction models. We tested three formulae for estimated glomerular filtration rate (eGFR) to determine the most clinically informative for predicting CVD and mortality. Using data from 440,526 participants from UK Biobank, eGFR was calculated using serum creatinine, cystatin C (eGFRcys) and creatinine-cystatin C. Associations of each eGFR with CVD outcome and mortality were compared using Cox models adjusting for atherosclerotic risk factors (per relevant risk scores), and predictive utility was determined by the C-statistic and categorical Net Reclassification Index. We show that eGFRcys is most strongly associated with CVD and mortality, and along with albuminuria adds predictive discrimination to current CVD risk scores, whilst traditional creatinine-based measures are weakly associated with risk. Clinicians should consider measuring eGFRcys as part of cardiovascular risk assessment. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

High–fat (HF) diet-induced obesity and insulin insensitivity are associated with inflammation, particularly in white adipose tissue (WAT). However, insulin insensitivity is apparent within days of HF feeding when gains in adiposity and changes in markers of inflammation are relatively minor. To investigate further the effects of HF diet, C57Bl/6J mice were fed either a low (LF) or HF diet for 3 days to 16 weeks, or fed the HF-diet matched to the caloric intake of the LF diet (PF) for 3 days or 1 week, with the time course of glucose tolerance and inflammatory gene expression measured in liver, muscle and WAT. HF fed mice gained adiposity and liver lipid steadily over 16 weeks, but developed glucose intolerance, assessed by intraperitoneal glucose tolerance tests (IPGTT), in two phases. The first phase, after 3 days, resulted in a 50% increase in area under the curve (AUC) for HF and PF mice, which improved to 30% after 1 week and remained stable until 12 weeks. Between 12 and 16 weeks the difference in AUC increased to 60%, when gene markers of inflammation appeared in WAT and muscle but not in liver. Plasma proteomics were used to reveal an acute phase response at day 3. Data from PF mice reveals that glucose intolerance and the acute phase response are the result of the HF composition of the diet and increased caloric intake respectively. Thus, the initial increase in glucose intolerance due to a HF diet occurs concurrently with an acute phase response but these effects are caused by different properties of the diet. The second increase in glucose intolerance occurs between 12 - 16 weeks of HF diet and is correlated with WAT and muscle inflammation. Between these times glucose tolerance remains stable and markers of inflammation are undetectable.