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1.
Nat Metab ; 3(2): 274-286, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33619379

RESUMO

The gut microbiome has important effects on human health, yet its importance in human ageing remains unclear. In the present study, we demonstrate that, starting in mid-to-late adulthood, gut microbiomes become increasingly unique to individuals with age. We leverage three independent cohorts comprising over 9,000 individuals and find that compositional uniqueness is strongly associated with microbially produced amino acid derivatives circulating in the bloodstream. In older age (over ~80 years), healthy individuals show continued microbial drift towards a unique compositional state, whereas this drift is absent in less healthy individuals. The identified microbiome pattern of healthy ageing is characterized by a depletion of core genera found across most humans, primarily Bacteroides. Retaining a high Bacteroides dominance into older age, or having a low gut microbiome uniqueness measure, predicts decreased survival in a 4-year follow-up. Our analysis identifies increasing compositional uniqueness of the gut microbiome as a component of healthy ageing, which is characterized by distinct microbial metabolic outputs in the blood.

3.
Nat Commun ; 11(1): 5997, 2020 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-33244003

RESUMO

The vitamin D receptor is highly expressed in the gastrointestinal tract where it transacts gene expression. With current limited understanding of the interactions between the gut microbiome and vitamin D, we conduct a cross-sectional analysis of 567 older men quantifying serum vitamin D metabolites using LC-MSMS and defining stool sub-Operational Taxonomic Units from16S ribosomal RNA gene sequencing data. Faith's Phylogenetic Diversity and non-redundant covariate analyses reveal that the serum 1,25(OH)2D level explains 5% of variance in α-diversity. In ß-diversity analyses using unweighted UniFrac, 1,25(OH)2D is the strongest factor assessed, explaining 2% of variance. Random forest analyses identify 12 taxa, 11 in the phylum Firmicutes, eight of which are positively associated with either 1,25(OH)2D and/or the hormone-to-prohormone [1,25(OH)2D/25(OH)D] "activation ratio." Men with higher levels of 1,25(OH)2D and higher activation ratios, but not 25(OH)D itself, are more likely to possess butyrate producing bacteria that are associated with better gut microbial health.

4.
Aging Cell ; 19(11): e13253, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33078901

RESUMO

The biological bases of longevity are not well understood, and there are limited biomarkers for the prediction of long life. We used a high-throughput, discovery-based proteomics approach to identify serum peptides and proteins that were associated with the attainment of longevity in a longitudinal study of community-dwelling men age ≥65 years. Baseline serum in 1196 men were analyzed using liquid chromatography-ion mobility-mass spectrometry, and lifespan was determined during ~12 years of follow-up. Men who achieved longevity (≥90% expected survival) were compared to those who died earlier. Rigorous statistical methods that controlled for false positivity were utilized to identify 25 proteins that were associated with longevity. All these proteins were in lower abundance in long-lived men and included a variety involved in inflammation or complement activation. Lower levels of longevity-associated proteins were also associated with better health status, but as time to death shortened, levels of these proteins increased. Pathway analyses implicated a number of compounds as important upstream regulators of the proteins and implicated shared networks that underlie the observed associations with longevity. Overall, these results suggest that complex pathways, prominently including inflammation, are linked to the likelihood of attaining longevity. This work may serve to identify novel biomarkers for longevity and to understand the biology underlying lifespan.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33059368

RESUMO

CONTEXT: Serum testosterone concentrations decline with age, while serum sex hormone-binding globulin (SHBG) concentrations increase. OBJECTIVE: To analyse associations of baseline serum testosterone and SHBG concentrations, and calculated free testosterone (cFT) values, with all-cause and cause-specific mortality in men. DESIGN, SETTING AND PARTICIPANTS: The UK Biobank prospective cohort study of community-dwelling men 40-69 years-old, followed for 11 years. MAIN OUTCOME MEASURES: All-cause, atherosclerotic cardiovascular disease (CVD) and cancer-related mortality. Cox proportional hazards regression was performed, adjusting for age, waist circumference, medical conditions and other covariates. Models for testosterone included SHBG, and vice versa. RESULTS: In complete case analysis of 149,436 men with 10,053 deaths (1,925 CVD and 4,927 cancer-related), men with lower testosterone had higher mortality from any cause (lowest vs highest quintile, Q1 vs Q5, fully-adjusted hazard ratio [HR]=1.14, 95% confidence interval [CI]=1.06-1.22, overall trend P<0.001), and cancer (HR=1.20, CI=1.09-1.33, P<0.001), with no association for CVD deaths. Similar results were seen for cFT. Men with lower SHBG had lower mortality from any cause (Q1 vs Q5, HR=0.68, CI=0.63-0.73, P<0.001), CVD (HR=0.70, CI=0.59-0.83, P<0.001), and cancer (HR=0.80, CI=0.72-0.89, P<0.001). A multiply-imputed dataset (N=208,425, 15,914 deaths, 3,128 CVD and 7,468 cancer-related) and analysis excluding deaths within first two years (9,261, 1,734 and 4,534 events) yielded similar results. CONCLUSIONS: Lower serum testosterone is independently associated with higher all-cause and cancer-related, but not CVD-related, mortality in middle-aged to older men. Lower SHBG is independently associated with lower all-cause, CVD-related and cancer-related mortality. Confirmation and determination of causality requires mechanistic studies and prospective trials.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32894755

RESUMO

BACKGROUND: We tested whether greater variation in red blood cell size, measured by red cell distribution width (RDW), may predict aging-related degenerative conditions and therefore, serve as a marker of biological aging. METHODS: 3,635 community-dwelling elderly men were enrolled in the prospective Osteoporotic Fractures in Men study (MrOS). RDW was categorized into 4 groups (≤13.0%, 13.1%-14.0%, 14.1%-15.0%, ≥15.1%). Functional limitations, frailty, strength, physical performance and cognitive function were measured at baseline and 7.4 years later. Falls were recorded in the year after baseline; hospitalizations were obtained for two years after baseline. Mortality were assessed during a mean of 8.3 years of follow-up. RESULTS: Participants with greater variability in red cell size were weaker, walked more slowly, and had worse cognitive function. They were more likely to have functional limitations (35.2% in the highest RDW category vs. 16.0% in the lowest, p & 0.001) and frailty (30.3% vs. 11.3%, p & 0.001). Those with greater variability in red cell size were more likely to develop new functional limitations and to become frail. The risk of having two or more falls was also greater (highest 19.2% vs. lowest 10.3%, p & 0.001). The risk of hospitalization was higher in those with highest variability (OR[95% CI], 1.8[1.3 - 2.5]) compared with the lowest. Variability in red cell size was related to total and cause-specific mortality. CONCLUSION: Greater variability in red cell size is associated with diverse aging-related outcomes, suggesting that it may have potential value as a marker for biological aging.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32979890

RESUMO

OBJECTIVE: Serum testosterone concentrations are affected by factors unrelated to hypothalamo-pituitary-testicular axis pathology. We evaluated the impact of sociodemographic, lifestyle and medical factors, on serum testosterone and sex hormone-binding globulin (SHBG) in men aged 40-69 years. DESIGN: Cross-sectional analysis of 208,677 community-dwelling men from the UK Biobank. MEASUREMENTS: We analysed associations of different factors with serum testosterone and SHBG (immunoassays) and calculated free testosterone (cFT), using smoothed centile plots, linear mixed models and effect size estimates. RESULTS: Median (interquartile range) for serum testosterone was 11.6 (9.4-14.1) nmol/L, SHBG 36.9 (27.9-48.1) nmol/L and cFT 213 (178-255) pmol/L. Age and BMI were inversely associated with testosterone and cFT, while SHBG was associated with age and inversely with BMI (all P < .001). Living with a partner, (South) Asian ethnicity, never or previous smoker and some medical conditions were associated with lower testosterone. Poultry or fish eater, and higher physical activity were associated with higher testosterone (all P < .001). Testosterone was lowered by ~0.5 nmol/L across ages, ~1.5 nmol/L for BMI 30 vs 25 kg/m2 , ~2 nmol/L for (South) Asian ethnicity, living with partner, college/university qualifications, low red meat eater, insufficient physical activity and 0.3-1.0 nmol/L with cardiovascular disease or diabetes. Different combinations of these factors varied serum testosterone by ~4 nmol/L, SHBG by ~30 nmol/L and cFT by ~60 pmol/L. CONCLUSIONS: The identified modifiable risk factors support lifestyle-based interventions in men with low testosterone concentrations. Considering sociodemographic, lifestyle and medical factors facilitates more personalized interpretation of testosterone testing results with respect to existing reference ranges.

8.
J Clin Endocrinol Metab ; 105(7)2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32364602

RESUMO

PURPOSE: The purpose of this work is to determine whether an uncoupling of bone turnover markers (BTMs) occurs in women exposed to the combination of sleep restriction with circadian disruption (SRCD), as previously reported in men. METHODS: Four bone biomarkers (N-terminal propeptide of type I procollagen [P1NP] and osteocalcin = bone formation; C-telopeptide [CTX] = bone resorption; sclerostin = bone formation inhibitor) were measured in bihourly samples over 24 hours at baseline and after approximately 3 weeks of sleep restriction (~5.6 hours of sleep/24 hours) with concurrent circadian disruption (SRCD, recurring 28-hour "day" in dim light). Maximum likelihood estimation in a repeated-measures model was used to assess the effects of SRCD and age on bone biomarkers. RESULTS: Five women were young (22 ±â€…2.8 years) and four were older (58 ±â€…1.8 years). Baseline bone biomarker levels did not differ by age (all P ≥ .07). Bone formation markers were lower after SRCD (estimate ±â€…SEE, ΔP1NP = -9.5 ±â€…2.8 µg/L, P = .01; Δosteocalcin = -2.3 ±â€…0.9 ng/mL, P = .04). The P1NP decline was greater in young women (ΔP1NP = -12.9 ±â€…3.7 µg/L, P = .01). After SRCD, CTX was significantly higher in young women (0.182 ±â€…0.069 ng/mL, P = .04) but did not change in older women. CONCLUSIONS: These pilot data are similar to previous findings in men and suggest that SRCD negatively altered bone metabolism in women by decreasing markers of bone formation and, in young women, increasing a marker of bone resorption. If sustained, this pattern of BTM uncoupling may lead to bone loss and lower bone mineral density.

9.
BMC Geriatr ; 20(1): 161, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32370738

RESUMO

BACKGROUND: Declines in bone, muscle and physical performance are associated with adverse health outcomes in older adults. However, few studies have described concurrent age-related patterns of change in these factors. The purpose of this study was to characterize change in four properties of muscle, physical performance, and bone in a prospective cohort study of older men. METHODS: Using repeated longitudinal data from up to four visits across 6.9 years from up to 4681 men (mean age at baseline 72.7 yrs. ±5.3) participating in the Osteoporotic Fractures in Men (MrOS) Study, we used group-based trajectory models (PROC TRAJ in SAS) to identify age-related patterns of change in four properties of muscle, physical performance, and bone: total hip bone mineral (BMD) density (g/m2) and appendicular lean mass/ht2 (kg/m2), by DXA; grip strength (kg), by hand dynamometry; and walking speed (m/s), by usual walking pace over 6 m. We also described joint trajectories in all pair-wise combinations of these measures. Mean posterior probabilities of placement in each trajectory (or joint membership in latent groups) were used to assess internal reliability of the model. The number of trajectories for each individual factor was limited to three, to ensure that the pair-wise determination of joint trajectories would yield a tractable number of groups as well as model fit considerations. RESULTS: The patterns of change identified were generally similar for all measures, with three district groups declining over time at roughly similar rates; joint trajectories revealed similar patterns with no cross-over or convergence between groups. Mean posterior probabilities for all trajectories were similar and consistently above 0.8 indicating reasonable model fit to the data. CONCLUSIONS: Our description of trajectories of change with age in bone mineral density, grip strength, walking speed and appendicular lean mass found that groups identified by these methods appeared to have little crossover or convergence of change with age, even when considering joint trajectories of change in these factors.

10.
J Am Med Dir Assoc ; 21(12): 1997-2002.e1, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32381425

RESUMO

OBJECTIVES: It is unknown whether muscle mass measured by the D3-creatine dilution method is a superior predictor of incident mobility disability than traditional components of sarcopenia definitions (including grip strength, walking speed, appendicular lean mass). The objective of this study was to determine the relative importance of strength; physical performance; and lean, fat, and muscle mass in predicting incident mobility disability in older men. DESIGN: Longitudinal cohort study of participants in the Osteoporotic Fractures in Men (MrOS) study. SETTING AND PARTICIPANTS: Muscle mass was assessed by D3-creatine dilution in 1098 men (aged 83.7 ± 3.7 years). Participants also completed anthropomorphic measures, 6-m walking speed (m/s), grip strength (kg), chair stands (seconds), and dual x-ray absorptiometry appendicular lean mass (ALM), and total body fat percentage. Men self-reported incident mobility disability defined by the development of an inability to complete at least one of walking 2-3 blocks, climbing 10 steps, or carrying 10 lb over 2.2 ± 0.3 years. METHODS: Classification and regression tree analysis was conducted to determine relative variable importance and algorithm cutpoints for predicting incident mobility disability. Given the proximity of walking speed with the primary outcome (mobility disability), analyses were conducted with and without walking speed. RESULTS: Walking speed followed by D3Cr muscle mass/weight were the most important variables (variable importance: 53% and 12%, respectively) in the prediction of self-reported incident mobility disability. D3Cr muscle mass was the most important variable in predicting incident mobility disability when walking speed was excluded, followed by chair stands (variable importance: 35% and 33%, respectively). Body fat percentage, ALM, and grip strength were not selected as nodes in either analysis and had low or negligible variable importance. CONCLUSIONS AND IMPLICATIONS: This study has provided valuable insights into the importance of different variables in predicting incident mobility disability in older men. Muscle mass by D3Cr may be a key tool for predicting the risk of negative outcomes in older adults in the future, particularly in post-acute and long-term care settings.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32442245

RESUMO

BACKGROUND: Whether low muscle mass is a risk factor for disability and mortality is unclear. Associations between approximations of muscle mass (including lean mass from dual energy x-ray absorptiometry (DXA)) and these outcomes are inconsistent. METHODS: Muscle mass measured by deuterated creatine (D3Cr) dilution and appendicular lean mass (ALM, by DXA) were assessed at the Year 14 Visit (2014-6) of the prospective MrOS study (N=1425, age 77-101 years). Disability in activities of daily living (ADLs), instrumental ADLS (IADLs), and mobility tasks was self-reported at the Year 14 visit and 2.2 years later; deaths were centrally adjudicated over 3.3 years. Relative risks (RR) and 95% confidence intervals (CI) were estimated per standard deviation decrement with negative binomial, logistic regression or proportional hazards models. RESULTS: In age and clinical center adjusted models, the RR per decrement in D3Cr muscle mass/wgt was 1.9 (95% CI: 1.2, 3.1) for incident self-reported ADL disability; 1.5 (95% CI: 1.3, 1.9) for IADL disability; and 1.8 (95% CI: 1.5, 2.2) for mobility disability. In age, clinical center and weight adjusted models, the RR per decrement in D3Cr muscle mass was 1.8 (95% CI: 1.5, 2.2) for all-cause mortality. In contrast, lower DXA ALM was not associated with any outcome. Associations of D3Cr muscle mass with these outcomes were slightly attenuated after adjustment for confounding factors and the potentially mediating effects of strength and physical performance. CONCLUSIONS: Low muscle mass as measured by D3Cr dilution is a novel risk factor for clinically meaningful outcomes in older men.

12.
J Gerontol A Biol Sci Med Sci ; 75(7): 1362-1368, 2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32436565

RESUMO

BACKGROUND: The combination of sarcopenia and obesity has been associated with physical impairment in older people. However, previous research has relied on assessments of lean mass as a surrogate for muscle mass. We postulate that inaccurate measures of muscle mass may have obscured the role of obesity in sarcopenia and related outcomes. Our aim was to clarify the interactions of muscle and fat with physical performance and adverse outcomes using an accurate measure of muscle mass. METHODS: In a longitudinal study of >1,300 older men (mean age 84 years), we compared a direct measurement of muscle mass (D3 creatine dilution; D3Cr) with an approximation of muscle mass (appendicular lean mass [ALM] by dual-energy x-ray absorptiometry [DXA]) and their associations with measures of physical performance (gait speed, chair stand time) and adverse outcomes (incident injurious falls and mobility problems). We measured percent fat mass by DXA. RESULTS: Low D3Cr muscle mass was strongly associated with decreased performance and increased risk of adverse outcomes. Increased fat mass had little association after accounting for D3Cr muscle mass. In contrast, DXA ALM was minimally associated with performance or adverse outcomes, and fatness remained associated with both outcomes after accounting for DXA ALM. CONCLUSIONS: When an accurate assessment of muscle mass (rather than lean mass) is used, reduced muscle mass is highly associated with important outcomes and the negative effects of adiposity are minimal, suggesting that obesity has little relevance for the understanding of important adverse health outcomes of sarcopenia in older men.

13.
BMJ Open ; 10(5): e034777, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32398333

RESUMO

INTRODUCTION: This study aims to clarify the role(s) of endogenous sex hormones to influence health outcomes in men, specifically to define the associations of plasma testosterone with incidence of cardiovascular events, cancer, dementia and mortality risk, and to identify factors predicting testosterone concentrations. Data will be accrued from at least three Australian, two European and four North American population-based cohorts involving approximately 20 000 men. METHODS AND ANALYSIS: Eligible studies include prospective cohort studies with baseline testosterone concentrations measured using mass spectrometry and 5 years of follow-up data on incident cardiovascular events, mortality, cancer diagnoses or deaths, new-onset dementia or decline in cognitive function recorded. Data for men, who were not taking androgens or drugs suppressing testosterone production, metabolism or action; and had no prior orchidectomy, are eligible. Systematic literature searches were conducted from 14 June 2019 to 31 December 2019, with no date range set for searches. Aggregate level data will be sought where individual participant data (IPD) are not available. One-stage IPD random-effects meta-analyses will be performed, using linear mixed models, generalised linear mixed models and either stratified or frailty-augmented Cox regression models. Heterogeneity in estimates from different studies will be quantified and bias investigated using funnel plots. Effect size estimates will be presented in forest plots and non-negligible heterogeneity and bias investigated using subgroup or meta-regression analyses. ETHICS AND DISSEMINATION: Ethics approvals obtained for each of the participating cohorts state that participants have consented to have their data collected and used for research purposes. The Androgens In Men Study has been assessed as exempt from ethics review by the Human Ethics office at the University of Western Australia (file reference number RA/4/20/5014). Each of the component studies had obtained ethics approvals; please refer to respective component studies for details. Research findings will be disseminated to the scientific and broader community via the publication of four research articles, with each involving a separate set of IPD meta-analyses (articles will investigate different, distinct outcomes), at scientific conferences and meetings of relevant professional societies. Collaborating cohort studies will disseminate findings to study participants and local communities. PROSPERO REGISTRATION NUMBER: CRD42019139668.

15.
JBMR Plus ; 4(3): e10335, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32161841

RESUMO

Worldwide, one in five men aged over 50 years will experience osteoporosis or a clinical bone fracture, with a greater fracture-related mortality rate than women. However, the genetic etiology of osteoporosis in men is still poorly understood. We aimed to identify the genetic variants and candidate genes associated with extremely low or high BMD for a better understanding of the biology underlying low bone density that may point to potential therapeutic targets for increasing bone mass. Subjects from the Osteoporotic Fractures in Men Study (MrOS) cohort were evaluated by age and BMI-adjusted total hip BMD. Those with BMD values 3 SDs away from the mean were selected and the remaining individuals whose adjusted BMD ranked at the highest or lowest 100 were included. Men with the lowest adjusted BMD (N = 98) and highest adjusted BMD (N = 110) were chosen for exome sequencing. Controls (N = 82) were men of Northern and Western European descent from the US Utah population of the 1000 Genomes Project. Fisher's exact test was performed to compare low- or high-BMD subjects with controls for single-gene associations. Additionally, sets of candidate genes causative of heritable disorders of connective tissue, including osteogenesis imperfecta (OI) and Ehlers-Danlos syndrome (EDS), were grouped for multigene and mutation burden analyses. No single-gene associations with rare variants were found for either the low BMD group (33 genes) or high BMD group (18 genes). In the group of OI genes, we detected a significant threefold increased accumulation of rare variants in low-BMD subjects compared with controls (p = 0.009). Additionally, genes associated with EDS had a twofold increased frequency in low-BMD subjects compared with controls (p = 0.03). These findings reveal a rare variant burden in OI and EDS disease genes at low BMD, which suggests a potential gene-panel approach to screen for multivariant associations in larger cohorts. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

16.
J Bone Miner Res ; 35(5): 869-874, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31991005

RESUMO

Red cell distribution width (RDW), routinely assessed as a component of a complete blood count (CBC), quantifies the variation in the size of red blood cells. It increases with age, and increased RDW predicts many aging-related diseases and mortality. However, whether it also predicts hip fracture is unknown. We prospectively evaluated the association between RDW and hip fracture using data from the Osteoporotic Fracture in Men (MrOS) study. RDW was measured in 3635 men (aged 71 to 99 years) along with bone mineral density (BMD) in MrOS. RDW ranged from 11.3% to 32.9% (median 14.0%; interquartile range 13.5% to 14.8%) and was categorized into four groups (≤13.0%, 13.1% to 14.0%, 14.1% to 15.0%, ≥15.1%). Study participants with a hemoglobin level <13.0 g/dL were classified as having anemia. During an average 8.1 years, 164 men suffered hip fractures. The risks of hip fractures increased with increase of RDW category. Furthermore, there was a significant interaction between anemia and RDW: An association between RDW and hip fractures was only observed in participants without anemia. In those without anemia, the relative hazard of hip fractures increased with increases in RDW category: Men in the highest RDW category had a 2.8 times higher risk of hip fractures than men in the lowest group (95% confidence interval 1.1 to 7.1). The risks of all-clinical fractures were also increased along with higher RDW values. Additionally, RDW was significantly associated with the risk of having a fall but not with femoral neck or total hip BMD. In conclusion, RDW and anemia defined by hemoglobin are widely available routine laboratory measurements that together could indicate increased risk of hip fracture, reflecting the neuromuscular effects of aging rather than lower hip BMD. © 2020 American Society for Bone and Mineral Research.

17.
J Cachexia Sarcopenia Muscle ; 11(1): 55-61, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31621207

RESUMO

BACKGROUND: Muscle mass declines with age. However, common assessments used to quantify muscle mass are indirect. The D3 -creatine (D3 Cr) dilution method is a direct assessment of muscle mass; however, longitudinal changes have not been examined in relation to changes in other measures of muscle mass, strength, and performance. METHODS: A convenience sample of 40 men from the Osteoporotic Fractures in Men Study (mean age = 83.3 years, standard deviation = 3.9) underwent repeat assessment of D3 Cr muscle mass, dual-energy X-ray absorptiometry (DXA) lean mass, grip strength, and walking speed at two time points approximately 1.6 years apart (2014-2016). One-sample t-tests and Pearson correlations were used to examine changes in DXA total body lean mass, DXA appendicular lean mass/height2 , DXA appendicular lean mass/weight, D3 Cr muscle mass, D3 Cr muscle mass/weight, grip strength, walking speed, and weight. RESULTS: D3 -creatine muscle mass, D3 Cr muscle mass/weight, grip strength, and walking speed all significantly declined (all P < 0.01). The change in DXA measures of lean mass was moderately correlated with changes in D3 Cr muscle mass. There was no significant correlation between the change in DXA measures of lean mass and change in walking speed (all P > 0.05). The change in D3 Cr muscle mass/weight was moderately correlated with change in walking speed (r = 0.33, P < .05). The change in grip strength was weakly correlated with the change in DXA measures of lean mass and D3 Cr muscle mass (r = 0.19-0.32). CONCLUSIONS: The results of our study provide new insights regarding the decline in muscle strength and D3 Cr muscle mass. The D3 Cr method may be a feasible tool to measure declines in muscle mass over time.

18.
Bone ; 132: 115198, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31866494

RESUMO

Our aim was to determine the association between objectively measured physical activity (PA) and bone strength of the distal limbs among older men. We studied 994 men from the MrOS cohort study (mean age 83.9) who had repeat (Year 7 and 14) 5-day activity assessment with at least 90% wear time (SenseWearPro3 Armband) and Year 14 measures using high resolution peripheral quantitative tomography (HR-pQCT) (Scanco). Total energy expenditure (TEE), total steps per day, peak cadence (mean of top 30 steps/min over 24 h) and time spent in a given level of activity: sedentary (reference, <1.5 metabolic equivalents of task [METs]), light (1.5 to <3 METs), or moderate to vigorous physical activity(MVPA: ≥3 METs) were calculated as mean over the two time points. Estimated failure load was determined from HR-pQCT data using finite element analysis. We used standardized variables and adjusted for potential confounders using linear regression. The means ±SDs for daily activity were: 2338 ± 356 kcal/d [TEE]; 5739 ± 2696 steps/day [step count], 60 ± 20 cpm [peak cadence], 67 ± 28 min/d [light activity], and 85 ± 52 min/d [MVPA]. Higher TEE, step count, and peak cadence were each associated with higher failure load of the distal radius (effect sizes respectively: 0.13 [95% CI: 0.05, 0.20], 0.11 [95% CI: 0.04, 0.18], and 0.08 [95% CI: 0.01, 0.15]) and higher failure load of the distal tibia (effect sizes respectively 0.21 [95% CI: 0.13, 0.28], 0.19 [95% CI: 0.13, 0.26], 0.19 [95% CI, 0.13, 0.25]). Time spent in MVPA vs. time sedentary was related to bone strength at both sites after adjustment, whereas time spent in light activity vs. time sedentary was not. TEE was associated with compartmental area and BMD parameters at distal tibia, but only area parameters at the distal radius. In summary, MVPA over a 7-year period of time may have a modest association with bone strength and geometry among older men.

19.
Am J Clin Nutr ; 110(4): 1003-1014, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31504105

RESUMO

BACKGROUND: While the gut microbiota is relatively stable through adulthood, its composition is influenced by various host and environmental factors, including changes in health, gastrointestinal processes (e.g., transit time, gastric acidity), medication use, and diet. The association of habitual diet, in the form of a posteriori-derived dietary patterns, and microbiota composition has not been adequately studied, particularly in older men. OBJECTIVE: The objective was to investigate the association of dietary patterns with the composition and diversity of the gut bacterial microbiota in community-dwelling, older men. METHODS: This cross-sectional study included 517 men who were participants in the Osteoporotic Fractures in Men (MrOS) Study (≥65 y of age at baseline in 2000-2002) and who provided a stool sample and completed an FFQ at MrOS Visit 4 in 2014-2016. Dietary patterns were derived by factor analysis. 16S ribosomal RNA target gene sequencing was performed and taxonomy assignments were derived using the Greengenes database. Linear regression and permutational multivariate analysis of variance (PERMANOVA) considered variations in alpha and beta diversity by dietary pattern, and a model that implements a 0-inflated Gaussian distribution of mean group abundance for each taxa (metagenomeSeq) assessed taxonomic variations by dietary pattern. RESULTS: In multivariable-adjusted models, greater adherence to the Western pattern was positively associated with families Mogibacteriaceae and Veillonellaceae and genera Alistipes, Anaerotruncus, CC-115, Collinsella, Coprobacillus, Desulfovibrio, Dorea, Eubacterium, and Ruminococcus, while greater adherence to the prudent pattern was positively associated with order Streptophyta, family Victivallaceae, and genera Cetobacterium, Clostridium, Faecalibacterium, Lachnospira, Paraprevotella, and Veillonella. The relative abundance of the dominant gut bacterial phyla, Bacteroidetes and Firmicutes, did not differ between participants with greater adherence to the Western pattern, compared with those with greater adherence to the prudent pattern. Dietary patterns were not associated with measures of alpha diversity, but beta diversity measures were significantly associated with both Western and prudent patterns. CONCLUSIONS: We observed significant associations between dietary patterns and measures of gut microbial composition in this sample of community-dwelling, older men.


Assuntos
Dieta , Microbioma Gastrointestinal , Vida Independente , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Humanos , Masculino
20.
Bone ; 126: 18-26, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30954730

RESUMO

Proteins are an essential part of essentially all biological processes, and there is enormous variation in protein forms and concentrations that is not reflected in DNA or RNA. Recently there have been rapid advances in the ability to measure protein sequence, modification and concentration, particularly with methods based in mass spectrometry. Global measures of proteins in tissues or in the circulation provide a broad assessment of the proteome that can be extremely useful for discovery, and targeted proteomic measures can yield specific and sensitive assessments of specific peptides and proteins. While most proteomic measures are directed at the detection of consensus peptide sequences, mass spectrometry based proteomic methods also allow a detailed examination of the peptide sequence differences that result from genetic variants and that may have important effects on protein function. In evaluating proteomic data, a number of analytical considerations are important, including an understanding of missing data, the challenge of multiple testing and replication, and the use of rapidly evolving methods in systems biology. While proteomics has not yet had a major impact in skeletal research, interesting recent research has used these approaches in the study of bone cell biology and the discovery of biomarkers of skeletal disorders. Proteomics can be expected to have an increasing influence in the study of bone biology and pathophysiology.


Assuntos
Osso e Ossos/metabolismo , Saúde , Proteômica , Análise de Dados , Humanos , Espectrometria de Massas , Biologia de Sistemas
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