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1.
Artigo em Inglês | MEDLINE | ID: mdl-33326040

RESUMO

CONTEXT: Follicle stimulating hormone (FSH) concentrations increase during the perimenopausal transition and remain high post menopause. Loss of bone mineral density (BMD) and gain of bone marrow adiposity (BMA) and body fat mass also occur during this time. In mice, blocking the action of FSH increases bone mass and decreases fat mass. OBJECTIVE: To investigate the associations between endogenous FSH levels and BMD, BMA and body composition in older adults, independent of estradiol and testosterone levels. DESIGN, SETTING AND PARTICIPANTS: Older adults from the AGES-Reykjavik Study, an observational cohort study. MAIN OUTCOME MEASURES: Areal BMD, total body fat, and lean mass were measured with DXA. Lumbar vertebral BMA was measured by 1H-MRS. Volumetric BMD and visceral and subcutaneous adipose tissue (VAT, SAT) areas were measured with QCT. The least squares means procedure was used to determine sex-hormone adjusted associations between quartiles of serum FSH and BMD, BMA, and body composition. RESULTS: In women (N=238, mean age 81y), those in the highest FSH quartile, compared with the lowest quartile, had lower adjusted mean spine integral BMD (-8.6%), lower spine compressive strength index (-34.8%), higher BMA (+8.4%), lower weight (-8.4%), lower VAT (-17.6%), lower lean mass (-6.1%), and lower fat mass (-11.9%) (all P < 0.05). In men, FSH level was not associated with any outcome. CONCLUSIONS: Older postmenopausal women with higher FSH levels have higher BMA, but lower BMD and lower fat and lean mass, independent of estradiol and testosterone levels. Longitudinal studies are needed to better understand the underlying mechanisms.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33231259

RESUMO

CONTEXT: Glycogen storage diseases are rare. Increased glycogen in the liver results in increased attenuation. OBJECTIVE: Investigate the association and function of a noncoding region associated with liver attenuation but not histologic nonalcoholic fatty liver disease. DESIGN: Genetics of Obesity-associated Liver Disease Consortium. SETTING: Population-based Main Outcome: Computed tomography measured liver attenuation. RESULTS: Carriers of rs4841132-A (frequency 2-19%) do not show increased hepatic steatosis; they have increased liver attenuation indicative of increased glycogen deposition. rs4841132 falls in a noncoding RNA LOC157273 ~190kb upstream of PPP1R3B. We demonstrate that rs4841132-A increases PPP1R3B through a cis genetic effect. Using CRISPR/Cas9 we engineered a 105bp deletion including rs4841132-A in human hepatocarcinoma cells which increases PPP1R3B, decreases LOC157273 and increases glycogen perfectly mirroring the human disease. Overexpression of PPP1R3B or knockdown of LOC157273 increased glycogen but did not result in decreased LOC157273 or increased PPP1R3B, respectively, suggesting that the effects may not all occur via affecting RNA levels. Based on EHR data, rs4841132-A associates with all components of the metabolic syndrome (MetS). However, rs4841132-A associated with decreased low-density lipoprotein (LDL) cholesterol and risk for myocardial infarction (MI). A metabolic signature for rs4841132-A includes increased glycine, lactate, triglycerides and decreased acetoacetate and beta-hydroxybutyrate. CONCLUSIONS: These results show that rs4841132-A promotes a hepatic glycogen storage disease by increasing PPP1R3B and decreasing LOC157273. rs4841132-A promotes glycogen accumulation and development of MetS but lowers LDL cholesterol and risk for MI. These results suggest that elevated hepatic glycogen is one cause of MetS that does not invariably promote MI.

3.
PLoS One ; 15(11): e0230035, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33186364

RESUMO

BACKGROUND: Genome-wide association studies have identified multiple genomic loci associated with coronary artery disease, but most are common variants in non-coding regions that provide limited information on causal genes and etiology of the disease. To overcome the limited scope that common variants provide, we focused our investigation on low-frequency and rare sequence variations primarily residing in coding regions of the genome. METHODS AND RESULTS: Using samples of individuals of European ancestry from ten cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, both cross-sectional and prospective analyses were conducted to examine associations between genetic variants and myocardial infarction (MI), coronary heart disease (CHD), and all-cause mortality following these events. For prevalent events, a total of 27,349 participants of European ancestry, including 1831 prevalent MI cases and 2518 prevalent CHD cases were used. For incident cases, a total of 55,736 participants of European ancestry were included (3,031 incident MI cases and 5,425 incident CHD cases). There were 1,860 all-cause deaths among the 3,751 MI and CHD cases from six cohorts that contributed to the analysis of all-cause mortality. Single variant and gene-based analyses were performed separately in each cohort and then meta-analyzed for each outcome. A low-frequency intronic variant (rs988583) in PLCL1 was significantly associated with prevalent MI (OR = 1.80, 95% confidence interval: 1.43, 2.27; P = 7.12 × 10-7). We conducted gene-based burden tests for genes with a cumulative minor allele count (cMAC) ≥ 5 and variants with minor allele frequency (MAF) < 5%. TMPRSS5 and LDLRAD1 were significantly associated with prevalent MI and CHD, respectively, and RC3H2 and ANGPTL4 were significantly associated with incident MI and CHD, respectively. No loci were significantly associated with all-cause mortality following a MI or CHD event. CONCLUSION: This study identified one known locus (ANGPTL4) and four new loci (PLCL1, RC3H2, TMPRSS5, and LDLRAD1) associated with cardiovascular disease risk that warrant further investigation.

4.
Exp Gerontol ; : 111172, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33245997

RESUMO

BACKGROUND: Weight-bearing jump tests that measure lower-extremity muscle power may be more strongly related to physical performance measures vs. non-weight-bearing leg press power, leg press strength and grip strength. We investigated if multiple muscle function measures differentially related to standard physical performance measures. MATERIALS/METHODS: In the Developmental Epidemiologic Cohort Study (DECOS; N = 68; age 78.5 ±â€¯5.5 years; 57% women; 7% minorities), muscle function measures included power in Watts/kg (functional, weight-bearing: jump; mechanical: Nottingham power rig; Keiser pneumatic leg press) and strength in kg/kg body weight (Keiser pneumatic leg press; hand-held dynamometry). Physical performance outcomes included 6 m usual gait speed (m/s), usual-paced 400 m walk time (seconds), and 5-repeated chair stands speed (stands/s). RESULTS: Women (N = 31; 79.8 ±â€¯5.0 years) had lower muscle function and slower gait speed compared to men (N = 25; 78.7 ±â€¯6.6 years), though similar 400 m walk time and chair stands speed. In partial Pearson correlations adjusted for age, sex, race and height, muscle function measures were moderately to strongly correlated with each other (all p < 0.05), though the individual correlations varied. In multiple regression analyses, each muscle function measure was statistically associated with all physical performance outcomes in models adjusted for age, sex, race, height, self-reported diabetes, self-reported peripheral vascular disease and self-reported pain in legs/feet (all p < 0.05). Jump power (ß = 0.75) and grip strength (ß = 0.71) had higher magnitudes of association with faster gait speed than lower-extremity power and strength measures (ß range: 0.32 to 0.7158). Jump power (ß = 0.56) had a slightly lower magnitude of association with faster 400 m walk time vs. Keiser power70% 1-RM (ß = 0.61), and a higher magnitude of association vs. Nottingham power, Keiser strength and grip strength (ß range: 0.41 to 0.47). Jump power (ß = 0.38) had a lower magnitude of association with chair stands speed than any other power or strength measures (ß range: 0.50 to 0.65). CONCLUSIONS: Jump power/kg and grip strength/kg may be more strongly related to faster gait speed, a standard measure of physical function and vital sign related to disability and mortality in older adults, compared to leg press power/strength. However, jump power/kg had a similar magnitude of association with 400 m walk time as Keiser power70% 1-RM/kg and a lower magnitude of association with faster chair stands speed than the other muscle function measures. Importantly, choice of muscle function measures should carefully reflect the study focus and methodologic considerations, including population.

5.
J Bone Miner Res ; 2020 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-33249669

RESUMO

Genetic studies of bone mineral density (BMD) largely have been conducted in European populations. We therefore conducted a meta-analysis of six independent African ancestry cohorts to determine whether previously reported BMD loci identified in European populations were transferable to African ancestry populations. We included nearly 5,000 individuals with both genetic data and assessments of BMD. Genotype imputation was conducted using the 1000G reference panel. We assessed SNP associations with femoral neck and lumbar spine BMD in each cohort separately, then combined results in fixed effects (or random effects if study heterogeneity was high, I2 index > 60) inverse variance weighted meta-analyses. In secondary analyses, we conducted locus-based analyses of rare variants using SKAT-O. Mean age ranged from 12 to 68 years. One cohort included only men and another cohort included only women; proportion of women in the other four cohorts ranged from 52% to 63%. Of 56 BMD loci tested, one locus, 6q25 (C6orf97, P-value=8.87×10-4 ) was associated with lumbar spine BMD and two loci, 7q21 (SLC25A13, P-value=2.84×10-4 ) and 7q31 (WNT16, P-value=2.96×10-5 ) were associated with femoral neck BMD. Effects were in the same direction as previously reported in European ancestry studies and met a Bonferroni-adjusted P-value threshold, the criteria for transferability to African ancestry populations. We also found associations that met locus-specific Bonferroni-adjusted P-value thresholds in 11q13 (LRP5, P-values<2.23×10-4 ), 11q14 (DCDC5, P-values<5.35×10-5 ), and 17p13 (SMG6, P-values<6.78×10-5 ) that were not tagged by European ancestry index SNPs. Rare single nucleotide variants in AKAP11 (P-value=2.32×10-2 ), MBL2 (P-value=4.09×10-2 ), MEPE (P-value=3.15×10-2 ), SLC25A13 (P-value=3.03×10-2 ), STARD3NL (P-value=3.35×10-2 ), and TNFRSF11A (P-value=3.18×10-3 ) were also associated with BMD. The majority of known BMD loci were not transferable. Larger genetic studies of BMD in African ancestry populations will be needed to overcome limitations in statistical power, and to identify both other loci that are transferable across populations and novel population-specific variants. This article is protected by copyright. All rights reserved.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32931633

RESUMO

BACKGROUND: This study aims to assess the construct validity of a body composition-defined definition of sarcopenic obesity based on low appendicular lean mass relative to fat mass (ALMIFMI ) and high fat mass index (FMI) and to compare with an alternative definition using appendicular lean mass index (ALMI) and percent body fat (%BF). METHODS: This is a secondary analysis of two cohort studies: the National Health and Examination Survey (NHANES) and the Health, Aging, and Body Composition study (Health ABC). Sarcopenic obesity was defined as low ALMIFMI combined with high FMI and was compared with a widely used definition based on ALMI and %BF cut-points. Body composition Z-scores, self-reported disability, physical functioning, and incident disability were compared across body composition categories using linear and logistic regression and Cox proportional hazards models. RESULTS: Among 14, 850 participants from NHANES, patients with sarcopenic obesity defined by low ALMIFMI and high FMI (ALMIFMI -FMI) had above-average FMI Z-scores [mean (standard deviation): 1.00 (0.72)]. In contrast, those with sarcopenic obesity based on low ALMI and high %BF (ALMI-%BF) had below-average FMI Z-scores. A similar pattern was observed for 2846 participants from Health ABC. Participants with sarcopenic obesity based on ALMIFMI -FMI had a greater number of disabilities, worse physical function, and a greater risk of incident disability compared with those defined based on ALMI-%BF. CONCLUSIONS: Body composition-defined measures of sarcopenic obesity defined as excess adiposity and lower-than-expected ALMI relative to FMI are associated with functional deficits and incident disability and overcome the limitations of using %BF in estimating obesity in this context.

7.
J Endocr Soc ; 4(5): bvz032, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32405607

RESUMO

Context: αKlotho is a hormone and co-receptor for fibroblast growth factor 23 (FGF23), a hormone that downregulates active vitamin D synthesis and promotes phosphate excretion. Low αKlotho and high FGF23 occur in chronic kidney disease (CKD). Objective: We aimed to assess the relationships of αKlotho and FGF23 with mobility disability in community-dwelling older adults. Design and Setting: We estimated associations of plasma-soluble αKlotho and serum FGF23 concentrations with mobility disability over 6 years. Additional analyses was stratified by CKD. Participants: Participants included 2751 adults (25.0% with CKD), aged 71 to 80 years, from the 1998 to 1999 Health, Aging, and Body Composition Study visit. Main Outcome Measures: Walking disability and stair climb disability were defined as self-reported "a lot of difficulty" or an inability to walk a quarter mile and climb 10 stairs, respectively. Results: Median (interquartile range [IQR]) serum FGF23 and plasma soluble αKlotho concentrations were 46.6 (36.7, 60.2) pg/mL and 630.4 (478.4, 816.0) pg/mL, respectively. After adjustment, higher αKlotho concentrations were associated with lower walking disability rates (Rate Ratio [RR] highest vs. lowest tertile = 0.74; 95% confidence interval l [CI] = 0.62, 0.89; P = 0.003). Higher FGF23 concentrations were associated with higher walking disability rates (RR highest vs. lowest tertile = 1.24; 95%CI = 1.03, 1.50; P = 0.005). Overall, higher αKlotho combined with lower FGF23 was associated with the lowest walking disability rates (P for interaction = 0.023). Stair climb disability findings were inconsistent. No interactions with CKD were statistically significant (P for interaction > 0.10). Conclusions: Higher plasma soluble αKlotho and lower serum FGF23 concentrations were associated with lower walking disability rates in community-dwelling older adults, particularly those without CKD.

8.
PLoS One ; 15(5): e0230815, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32379818

RESUMO

Smoking is a potentially causal behavioral risk factor for type 2 diabetes (T2D), but not all smokers develop T2D. It is unknown whether genetic factors partially explain this variation. We performed genome-environment-wide interaction studies to identify loci exhibiting potential interaction with baseline smoking status (ever vs. never) on incident T2D and fasting glucose (FG). Analyses were performed in participants of European (EA) and African ancestry (AA) separately. Discovery analyses were conducted using genotype data from the 50,000-single-nucleotide polymorphism (SNP) ITMAT-Broad-CARe (IBC) array in 5 cohorts from from the Candidate Gene Association Resource Consortium (n = 23,189). Replication was performed in up to 16 studies from the Cohorts for Heart Aging Research in Genomic Epidemiology Consortium (n = 74,584). In meta-analysis of discovery and replication estimates, 5 SNPs met at least one criterion for potential interaction with smoking on incident T2D at p<1x10-7 (adjusted for multiple hypothesis-testing with the IBC array). Two SNPs had significant joint effects in the overall model and significant main effects only in one smoking stratum: rs140637 (FBN1) in AA individuals had a significant main effect only among smokers, and rs1444261 (closest gene C2orf63) in EA individuals had a significant main effect only among nonsmokers. Three additional SNPs were identified as having potential interaction by exhibiting a significant main effects only in smokers: rs1801232 (CUBN) in AA individuals, rs12243326 (TCF7L2) in EA individuals, and rs4132670 (TCF7L2) in EA individuals. No SNP met significance for potential interaction with smoking on baseline FG. The identification of these loci provides evidence for genetic interactions with smoking exposure that may explain some of the heterogeneity in the association between smoking and T2D.


Assuntos
Glicemia/análise , Fumar Cigarros/genética , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Jejum/sangue , Genótipo , Adulto , Grupo com Ancestrais do Continente Africano/genética , Idoso , Fumar Cigarros/etnologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etnologia , Grupo com Ancestrais do Continente Europeu/genética , Estudos de Viabilidade , Feminino , Loci Gênicos , Estudo de Associação Genômica Ampla , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Risco
9.
Artigo em Inglês | MEDLINE | ID: mdl-32361748

RESUMO

BACKGROUND: Frailty is more prevalent among black versus white older Americans. We previously identified 37 metabolites associated with the vigor to frailty spectrum using the Scale of Aging Vigor in Epidemiology (SAVE) among older black men from the Health, Aging, and Body Composition (Health ABC) study. Here, we sought to develop a metabolite composite score based on the 37 SAVE-associated metabolites and determine whether the composite score predicts mortality and whether it attenuates the association between frailty and mortality among older black men. METHODS: Plasma metabolites were measured using liquid chromatography-mass spectrometry. Most of the 37 metabolites were organic acids/derivatives or lipids. Metabolites were ranked into tertiles: tertiles associated with more vigorous SAVE scores were scored zero, mid-tertiles were scored one, and tertiles associated with frailer SAVE scores were scored two. Composite scores were the sum of metabolite tertile scores. We examined mortality associations using Cox regression. Percent attenuation estimated the extent to which metabolites attenuated the association between frailty and mortality. RESULTS: One standard deviation frailer SAVE was associated with 30% higher mortality, adjusting for age and site (p=0.0002); this association was attenuated by 56% after additionally adjusting for the metabolite composite score. In this model, one standard deviation higher metabolite composite score was associated with 46% higher mortality (p<0.0001). Metabolite composite scores also predicted mortality (p=0.045) in a validation sample of 120 older adults (40% men, 90% white). CONCLUSION: These metabolites may provide a deeper characterization of the higher mortality that is associated with frailty among older adults.

10.
J Gerontol A Biol Sci Med Sci ; 75(12): 2434-2440, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-32267924

RESUMO

BACKGROUND: Poor sense of smell in older adults may lead to weight loss, which may further contribute to various adverse health outcomes. However, empirical prospective evidence is lacking. We aimed to longitudinally assess whether poor olfaction is associated with changes in body composition among older adults. METHODS: A total of 2,390 participants from the Health ABC Study had their olfaction assessed using the Brief Smell Identification Test in 1999-2000. Based on the test score, olfaction was defined as poor (0-8), moderate (9-10), or good (11-12). Total body mass, lean mass, and fat mass were measured by dual-energy X-ray absorptiometry annually or biennially from 1999 to 2007. RESULTS: At baseline, compared to participants with good olfaction, those with poor olfaction weighed on average 1.67 kg less (95% CI: -2.92, -0.42) in total mass, 0.53 kg less (95% CI: -1.08, 0.02) in lean mass, and 1.14 kg less (95% CI: -1.96, -0.31) in fat mass. In longitudinal analyses, compared to participants with good olfaction, those with poor olfaction had a greater annual decline in both total mass (-234 g, 95% CI: -442, -26) and lean mass (-139 g, 95% CI: -236, -43). They also tended to have a greater annual loss of fat mass (-113 g, 95% CI: -285, 59), but the difference was not statistically significant. CONCLUSIONS: Our results indicate poor olfaction is associated with lower body weight and greater weight loss in older adults. It is imperative for future studies to investigate potential underlying mechanisms and associated adverse health consequences.

11.
BMC Pediatr ; 20(1): 25, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964368

RESUMO

BACKGROUND: Obesity has been longitudinally associated with depression but only few studies take a life course approach. This longitudinal study investigates whether being overweight or obese at age 8 and 13 years is associated with depressive symptoms more than 60 years later and whether this association is independent of late-life body mass index (BMI). We also investigated the association of being overweight/obese at age 8 or 13 years with ever having major depressive disorder (lifetime MDD). METHOD: This analysis is based on a sub-sample of 889 AGES-Reykjavik participants with measured BMI data from early life. Late-life depressive symptoms were measured with the Geriatric Depression Scale (GDS) and lifetime MDD was assessed at late-life using the Mini International Neuropsychiatric Interview. Logistic regression analysis was used to estimate the relationships between BMI (continuous and categorical) at age 8 or 13 years, and late-life depressive symptoms (measured as GDS ≥ 5) or lifetime MDD, adjusted for sex, education, physical activity, smoking status and alcohol use. In a separate model, additional adjustments were made for late-life BMI. RESULTS: One hundred and one subjects (11%) had depressive symptoms at late-life (GDS ≥ 5), and 39 subjects (4.4%) had lifetime MDD. Being overweight or obese at age 8 or 13 years was not associated with higher depressive symptoms during late-life, irrespective of late-life BMI. Being overweight or obese at age 8 years, but not age 13 years was associated with an increased risk of lifetime MDD (Odds Ratio (OR) (95% confidence interval [CI]) for age 8 = 4.03[1.16-13.96]P = 0.03 and age 13 = 2.65[0.69-10.26] P = 0.16, respectively). CONCLUSION: Being overweight in childhood was associated with increased odds of lifetime MDD, although the magnitude of the risk is uncertain given the small numbers of participants with lifetime MDD. No clear association was observed between childhood and adolescent overweight/obesity and late-life depressive symptoms irrespective of late life BMI.

12.
J Bone Miner Res ; 35(2): 326-332, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31618468

RESUMO

Bone marrow adiposity (BMA) is associated with aging and osteoporosis, but whether BMA can predict bone loss and fractures remains unknown. Using data from the Age Gene/Environment Susceptibility (AGES)-Reykjavik study, we investigated the associations between 1 H-MRS-based measures of vertebral bone marrow adipose tissue (BMAT), annualized change in bone density/strength by quantitative computed tomography (QCT) and DXA, and secondarily, with incident clinical fractures and radiographic vertebral fractures among older adults. The associations between BMAT and annualized change in bone density/strength were evaluated using linear regression models, adjusted for age, body mass index (BMI), diabetes, estradiol, and testosterone. Cox proportional hazards models were used to evaluate the associations between baseline BMAT and incident clinical fractures, and logistic regression models for incident vertebral fractures. At baseline, mean ± SD age was 80.9 ± 4.2 and 82.6 ± 4.2 years in women (n = 148) and men (n = 150), respectively. Mean baseline BMAT was 55.4% ± 8.1% in women and 54.1% ± 8.2% in men. Incident clinical fractures occurred in 7.4% of women over 2.8 years and in 6.0% of men over 2.2 years. Incident vertebral fractures occurred in 12% of women over 3.3 years and in 17% of men over 2.7 years. Each 1 SD increase in baseline BMAT was associated with a 3.9 mg2 /cm4 /year greater loss of spine compressive strength index (p value = .003), a 0.9 mg/cm3 /year greater loss of spine trabecular BMD (p value = .02), and a 1.2 mg/cm3 /year greater loss of femoral neck trabecular BMD (p value = .02) in women. Among men, there were no associations between BMAT and changes in bone density/strength. There were no associations between BMAT and incident fractures in women or men. In conclusion, we found greater BMAT is associated with greater loss of trabecular bone at the spine and femoral neck, and greater loss of spine compressive strength, in older women. © 2019 American Society for Bone and Mineral Research.

13.
J Gerontol A Biol Sci Med Sci ; 75(3): 531-536, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-30561511

RESUMO

BACKGROUND: Depressive symptoms and hearing loss (HL) are independently associated with increased risk of incident disability; whether the increased risk is additive is unclear. METHODS: Cox Proportional Hazards models were used to assess joint associations of HL (normal, mild, moderate/severe) and late-life depressive symptoms (defined by a score of ≥8 on the 10-item Center for Epidemiologic Studies-Depression scale) with onset of mobility disability (a lot of difficulty or inability to walk » mile and/or climb 10 steps) and any disability in activities of daily living (ADL), among 2,196 participants of the Health, Aging and Body Composition Study, a cohort of well-functioning older adults aged 70-79 years. Models were adjusted for age, race, sex, education, diabetes, hypertension, and body mass index. RESULTS: Relative to participants with normal hearing and without depressive symptoms, participants without depressive symptoms who had mild or moderate/severe HL had increased risk of incident mobility and ADL disability (hazard ratio [HR] for mobility disability, mild HL:1.34, 95% confidence interval [CI]: 1.09, 1.64 and HR for mobility disability, moderate/severe HL: 1.37, 95% CI: 1.08, 1.75 and HR for ADL disability, mild HL: 1.32, 95% CI: 1.08, 1.63, and HR for ADL disability, moderate/severe HL: 1.42, 95% CI: 1.11, 1.82). Among participants with depressive symptoms, mild HL (HR: 1.71, 95% CI: 1.09, 2.70) was associated with increased risk of incident mobility disability. CONCLUSIONS: Independent of depressive symptoms, risk of incident disability was greater in older adults with HL, regardless of severity. Further research into HL interventions may delay disability onset.


Assuntos
Atividades Cotidianas , Envelhecimento , Composição Corporal , Depressão/complicações , Perda Auditiva/complicações , Limitação da Mobilidade , Fatores Etários , Idoso , Avaliação da Deficiência , Feminino , Humanos , Masculino , Estudos Prospectivos
14.
Nicotine Tob Res ; 22(6): 935-941, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-31091312

RESUMO

INTRODUCTION: In addition to well-established links with cardiovascular and respiratory diseases, cigarette smoking may affect skeletal muscle; however, associations with quadriceps atrophy, density, and function are unknown. This study explored the associations of current and former smoking with quadriceps muscle area and attenuation as well as muscle force (assessed as knee extension peak torque) and rate of torque development-a measure of muscle power in older adults. METHODS: Data from 4469 older adults, aged 66-95 years at baseline in the Age, Gene/Environment Susceptibility-Reykjavik Study with measurements of thigh computed tomography, isometric knee extension testing, self-reported smoking history, and potential covariates were analyzed. RESULTS: Sex differences were observed in these data; therefore, our final analyses are stratified by sex. In men, both former smokers and current smokers had lower muscle area (with ß= -0.10, 95% confidence interval [CI] = -0.17 to -0.03 and ß = -0.19, 95% CI = -0.33 to -0.05, respectively) and lower muscle attenuation (ie, higher fat infiltration, ß = -0.08, 95% CI = -0.16 to -0.01 and ß = -0.17, 95% CI = -0.34 to -0.01, respectively) when compared with never smokers. Smoking status was not associated with male peak torque or rate of torque development. In women, current smoking was associated with lower muscle attenuation (ß = -0.24, 95% CI = -0.34 to -0.13) compared to never smoking. Among female smokers (current and former), muscle attenuation and peak torque were lower with increasing pack-years. CONCLUSIONS: Results suggest that cigarette smoking is related to multiple muscle properties at older age and that these relationships may be different among men and women. IMPLICATIONS: This article presents novel data, as it examined for the first time the relationship between smoking and computed tomography-derived quadriceps muscle size (cross-sectional area) and attenuation. This study suggests that current cigarette smoking is related to higher muscle fat infiltration, which may have significant health implications for the older population, because of its known association with poor physical function, falls, and hip fractures.


Assuntos
Fumar Cigarros/efeitos adversos , Músculo Esquelético/patologia , Músculo Quadríceps/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/efeitos dos fármacos , Estudos Prospectivos , Músculo Quadríceps/diagnóstico por imagem , Músculo Quadríceps/efeitos dos fármacos , Fumantes , Tomografia Computadorizada por Raios X
15.
Aging Clin Exp Res ; 32(4): 587-595, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31853832

RESUMO

BACKGROUND/AIMS: Weight-bearing jump tests measure lower extremity muscle power, velocity, and force, and may be more strongly related to physical performance than grip strength. However, these relationships are not well described in older adults. METHODS: Participants were 1242 older men (mean age 84 ± 4 years) in the Osteoporotic Fractures in Men (MrOS) Study. Jump peak power (Watts/kg body weight), force (Newton/kg body weight) at peak power, and velocity (m/s) at peak power were measured by jump tests on a force plate. Grip strength (kg/kg body weight) was assessed by hand-held dynamometry. Physical performance included 400 m walk time (s), 6 m usual gait speed (m/s), and 5-repeated chair stands speed (#/s). RESULTS: In adjusted Pearson correlations, power/kg and velocity moderately correlated with all performance measures (range r = 0.41-0.51; all p < 0.001), while correlations for force/kg and grip strength/kg were weaker (range r = 0.20-0.33; all p < 0.001). Grip strength/kg moderately correlated with power/kg (r = 0.44; p < 0.001) but not velocity or force/kg. In adjusted linear regression with standardized ßs, 1 SD lower power/kg was associated with worse: 400 m walk time (ß = 0.47), gait speed (ß = 0.42), and chair stands speed (ß = 0.43) (all p < 0.05). Associations with velocity were similar (400 m walk time: ß = 0.42; gait speed: ß = 0.38; chair stands speed: ß = 0.37; all p < 0.05). Force/kg and grip strength/kg were more weakly associated with performance (range ß = 0.18-0.28; all p < 0.05). CONCLUSIONS/DISCUSSION: Jump power and velocity had stronger associations with physical performance than jump force or grip strength. This suggests lower extremity power and velocity may be more strongly related to physical performance than lower extremity force or upper extremity strength in older men.


Assuntos
Envelhecimento Saudável/fisiologia , Fraturas por Osteoporose/prevenção & controle , Desempenho Físico Funcional , Idoso de 80 Anos ou mais , Força da Mão/fisiologia , Humanos , Estudos Longitudinais , Extremidade Inferior/fisiologia , Masculino , Medição de Risco , Velocidade de Caminhada/fisiologia
16.
Stat Biosci ; 11(2): 210-237, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31762829

RESUMO

Wearable accelerometers provide detailed, objective, and continuous measurements of physical activity (PA). Recent advances in technology and the decreasing cost of wearable devices led to an explosion in the popularity of wearable technology in health research. An ever-increasing number of studies collect high-throughput, sub-second level raw acceleration data. In this paper, we discuss problems related to the collection and analysis of raw accelerometry data and refer to published solutions. In particular, we describe the size and complexity of the data, the within- and between-subject variability, and the effects of sensor location on the body. We also discuss challenges related to sampling frequency, device calibration, data labeling and multiple PA monitors synchronization. We illustrate these points using the Developmental Epidemiological Cohort Study (DECOS), which collected raw accelerometry data on individuals both in a controlled and the free-living environment.

17.
Nat Genet ; 51(11): 1580-1587, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31659325

RESUMO

Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P < 5.0 × 10-8). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification.


Assuntos
Aterosclerose/patologia , Predisposição Genética para Doença , Histona Desacetilases/metabolismo , Histona Desacetilases/fisiologia , Contração Muscular , Músculo Liso Vascular/patologia , Proteínas Repressoras/metabolismo , Proteínas Repressoras/fisiologia , Calcificação Vascular/patologia , Idoso , Animais , Aorta/metabolismo , Aorta/patologia , Aterosclerose/genética , Aterosclerose/metabolismo , Estudos de Coortes , Feminino , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , Estudo de Associação Genômica Ampla , Histona Desacetilases/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Músculo Liso Vascular/metabolismo , Fenótipo , Polimorfismo de Nucleotídeo Único , Proteínas Repressoras/genética , Calcificação Vascular/genética , Calcificação Vascular/metabolismo
18.
Front Public Health ; 7: 256, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31572702

RESUMO

Background: Little is known about the role of perceived neighborhood environment as a determinant of physical activity (PA) and sedentary time (ST) in understanding obesity-related health behaviors. We focus on a biracial, socioeconomically diverse population using objectively measured ST, which is under-represented in the literature. Methods: We examined the association between self-reported neighborhood perception (Likert-scale questions), PA using the Baecke questionnaire, and both non-sedentary time and ST using accelerometry from wave 4 of the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (n = 2,167). After applying exclusion criteria, the sample size was n = 1,359 for analyses of self-reported PA and n = 404 for analyses of accelerometry data. Factor analysis identified key neighborhood characteristics to develop a total neighborhood perception score (NPS). Higher NPS indicated less favorable neighborhood perception. Linear regression was used to determine the relationship between NPS, PA, non-sedentary time, and ST. Results: Complete data were available for n = 1,359 [age 56.6(9.0) years, 59.5% female, 62.2% African American] for whom we identified four neighborhood perception factors: (1) concern about crime, (2) physical environment, (3) location of violent crime, and (4) social environment. Worsening perception of the overall neighborhood [ß = -0.13 (SE = 0.03); p = 0.001], the physical environment [-0.11 (0.05); p = 0.03], and the social environment [-0.46 (0.07); p < 0.0001] were associated with decreased PA. Worsening perception of the overall neighborhood [1.14 (0.49); p = 0.02] and neighborhood social environment [3.59 (1.18); p = 0.003] were associated with increased ST over the day. There were no interactions for race, sex, poverty status, or economic index. Conclusion: Poor overall neighborhood perception, perceived social environment, and perceived neighborhood physical environment are associated with PA and ST in a multi-racial, socioeconomically diverse cohort of urban adults. Clinical Trial Registration: The HANDLS study is registered at ClinicalTrials.gov as NCT01323322.

20.
Cancer Causes Control ; 30(10): 1057-1065, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401707

RESUMO

PURPOSE: As obesity and type 2 diabetes (T2D) have been increasing worldwide, we investigated their association with breast cancer incidence in the Reykjavik Study. METHODS: During 1968-1996, approximately 10,000 women (mean age = 53 ± 9 years) completed questionnaires and donated blood samples. T2D status was classified according to self-report (n = 140) and glucose levels (n = 154) at cohort entry. A linkage with the Icelandic Cancer Registry provided breast cancer incidence through 2015. Cox regression with age as time metric and adjusted for known confounders was applied to obtain hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Of 9,606 participants, 294 (3.1%) were classified as T2D cases at cohort entry while 728 (7.8%) women were diagnosed with breast cancer during 28.4 ± 11.6 years of follow-up. No significant association of T2D (HR 0.95; 95% CI 0.56-1.53) with breast cancer incidence was detected except among the small number of women with advanced breast cancer (HR 3.30; 95% CI 1.13-9.62). Breast cancer incidence was elevated among overweight/obese women without (HR 1.18; 95% CI 1.01-1.37) and with T2D (HR 1.35; 95% CI 0.79-2.31). Height also predicted higher breast cancer incidence (HR 1.03; 95% CI 1.02-1.05). All findings were confirmed in women of the AGES-Reykjavik sub-cohort (n = 3,103) who returned for an exam during 2002-2006. With a 10% T2D prevalence and 93 incident breast cancer cases, the HR for T2D was 1.18 (95% CI 0.62-2.27). CONCLUSIONS: These findings in a population with low T2D incidence suggest that the presence of T2D does not confer additional breast cancer risk and confirm the importance of height and excess body weight as breast cancer risk factors.


Assuntos
Neoplasias da Mama/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Sobrepeso/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Islândia/epidemiologia , Incidência , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco
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