Dysregulated homeostatic pathways in sarcopenia among frail older adults.
Ontology highlight
ABSTRACT:
SUBMITTER: Ng TP
PROVIDER: S-EPMC6260914 | biostudies-literature | 2018 Dec
REPOSITORIES: biostudies-literature
Publications
Dysregulated homeostatic pathways in sarcopenia among frail older adults.
Ng Tze Pin TP Lu Yanxia Y Choo Robin Wai Mun RWM Tan Crystal Tze Ying CTY Nyunt Ma Shwe Z MSZ Gao Qi Q Mok Esther Wing Hei EWH Larbi Anis A
Aging cell 20181009 6
Sarcopenia, a core feature of the physical frailty syndrome, is characterized by multisystem physiological dysregulation. No study has explored qualitatively the hierarchical network of relationships among different dysregulated pathways involved in the pathogenesis of sarcopenia. We used 40 blood biomarkers belonging to community-dwelling prefrail and frail older persons to derive measures of multiple physiological pathways, and structural equation modeling to generate path network models of th ...[more]
Similar Datasets
Project description:BackgroundSarcopenia is common among older individuals with and without type 2 diabetes mellitus (T2DM). There are conflicting evidence in support of the role of insulin in the development of age-related and T2DM-related sarcopenia. We investigated the relationships between the levels of fasting insulin and other blood biomarkers related to insulin or lipid metabolism with the presence of sarcopenia in two independent studies.Materials and methodsIn 246 pre-frail frail older individuals with (n = 41) and without T2DM (n = 205) in the Singapore Frailty Interventional Trial, sarcopenia was defined by low appendicular lean mass (ALM) relative to total body mass (skeletal muscle index, SMI = ALM/height2) and low lower limb strength or gait speed according to the Asian Working Group for Sarcopenia (AWGS) criteria released in 2019, and related to levels of fasting insulin and glucose, C-peptide, IGF-1, leptin, and active ghrelin. This investigation was validated in another independent study sample of 189 robust and pre-frail frail elderly in the Singapore Longitudinal Aging Study Wave 2 (SLAS-2).ResultsCompared to non-sarcopenic individuals, those with sarcopenia and possible sarcopenia showed significantly lower fasting insulin (p < 0.05) in pre-frail/frail and non-frail older individuals. Consistent trends of relationships were observed for serum levels of C-peptide, IGF-1, leptin, and active ghrelin. In multivariable logistic regression models, sarcopenia was independently associated with low insulin (p < 0.05). Levels of fasting insulin, C-peptide, and leptin were also significantly associated with BMI, SMI, knee extension strength, gait speed, and physical activity score.ConclusionDysregulated insulin secretion in diabetic and non-diabetic older individuals may play an important role in age-related and diabetes-related sarcopenia.
| S-EPMC9722960 | biostudies-literature
Project description:IntroductionPhysical activity (PA) is important for healthy ageing. Better insight into objectively measured PA levels in older adults is needed, since most previous studies employed self-report measures for PA assessment, which are associated with overestimation of PA.AimThis study aimed to provide insight in objectively measured indoor and outdoor PA of older adults, and in PA differences by frailty levels.MethodsData were collected among non-frail (N = 74) and frail (N = 10) subjects, aged 65 to 89 years. PA, measured for seven days with accelerometers and GPS-devices, was categorized into three levels of intensity (sedentary, light, and moderate-to-vigorous PA).ResultsOlder adults spent most time in sedentary and light PA. Subjects spent 84.7%, 15.1% and 0.2% per day in sedentary, light and moderate-to-vigorous PA respectively. On average, older adults spent 9.8 (SD 23.7) minutes per week in moderate-to-vigorous activity, and 747.0 (SD 389.6) minutes per week in light activity. None of the subjects met the WHO recommendations of 150 weekly minutes of moderate-to-vigorous PA. Age-, sex- and health status-adjusted results revealed no differences in PA between non-frail and frail older adults. Subjects spent significantly more sedentary time at home, than not at home. Non-frail subjects spent significantly more time not at home during moderate-to-vigorous activities, than at home.ConclusionsObjective assessment of PA in older adults revealed that most PA was of light intensity, and time spent in moderate-to-vigorous PA was very low. None of the older adults met the World Health Organization recommendations for PA. These levels of MVPA are much lower than generally reported based on self-reported PA. Future studies should employ objective methods, and age specific thresholds for healthy PA levels in older adults are needed. These results emphasize the need for effective strategies for healthy PA levels for the growing proportion of older adults.
| S-EPMC4409218 | biostudies-literature
Project description:Vitamin D deficiency is common among older adults and has been linked to muscle weakness. Vitamin D supplementation has been proposed as a strategy to improve muscle function in older adults. The aim of this study was to investigate the effect of calcifediol (25-hydroxycholecalciferol) on whole genome gene expression in skeletal muscle of vitamin D deficient frail older adults. A double-blind placebo controlled trial was conducted in vitamin D deficient frail older adults (aged above 65), characterized by blood 25-hydroxycholecalciferol concentrations between 20 and 50 nmol/L. Subjects were randomized across the placebo group (n=12) and the calcifediol group (n=10, 10 µg per day). Muscle biopsies were obtained before and after six months of calcifediol or placebo supplementation and subjected to whole genome gene expression profiling using Affymetrix HuGene 2.1ST arrays. Expression of the vitamin D receptor gene was virtually undetectable in human skeletal muscle biopsies. Calcifediol supplementation led to a significant increase in blood 25-hydroxycholecalciferol levels compared to the placebo group. No difference between treatment groups was observed on strength outcomes. The whole transcriptome effects of calcifediol and placebo were very weak. Correcting for multiple testing using false discovery rate did not yield any differentially expressed genes using any sensible cut-offs. P-values were uniformly distributed across all genes, suggesting that low p-values are likely to be false positives. Partial least squares-discriminant analysis and principle component analysis was unable to separate treatment groups. Calcifediol supplementation did not affect the skeletal muscle transcriptome in frail older adults. Our findings indicate that vitamin D supplementation has no effects on skeletal muscle gene expression, suggesting that skeletal muscle may not be a direct target of vitamin D in older adults.
2019-06-10 | GSE123993 | GEO
Project description:Few studies have comprehensively described changes in blood biomarkers of the physiological responses underlying sarcopenia reduction associated with lifestyle interventions. In this study, we performed secondary analyses of data in a randomized controlled trial of multi-domain lifestyle interventions (6-month duration physical exercise, nutritional enrichment, cognitive training, combination and standard care control) among 246 community-dwelling pre-frail and frail elderly, aged ≥65 years, with and without sarcopenia. Appendicular lean mass (ALM), lower limb strength, gait speed, and blood levels of markers of muscle metabolism, inflammation, anti-oxidation, anabolic hormone regulation, insulin signaling, tissue oxygenation were measured at baseline, 3-month and 6-month post-intervention. Multi-domain interventions were associated with significant (p < 0.001) reduction of sarcopenia at 3-month and 6-month post-intervention, improved gait speed, enhanced lower limb strength, and were equally evident among sarcopenic participants who were slower at baseline than non-sarcopenic participants. Active intervention was associated with significantly reduced inflammation levels. Sarcopenia status and reduction were associated with blood biomarkers related to muscle metabolism, steroid hormone regulation, insulin-leptin signaling, and tissue oxygenation. Physical, nutritional and cognitive intervention was associated with measures of sarcopenia reduction, together with changes in circulating biomarkers of anabolic and catabolic metabolism underlying sarcopenia.
| S-EPMC8064206 | biostudies-literature
Project description:BACKGROUND:As the number of older adults increases, so does the number of frail older adults. Although anthropometry has been widely used as a way to stratify the overall mortality risk of a person, the significance of these measurements becomes blurred in the case of frail older adults who have changes in body composition. Therefore, the aim of this study is to determine the association of anthropometric measurements (body mass index, knee-adjusted height body mass index, waist-to-hip ratio and calf circumference) with mortality risk in a group of older Mexican adults. METHODS:This is a longitudinal analysis of the Mexican Health and Aging sub-sample (with biomarkers, n = 2573) from the first wave in 2001, followed-up to the last available wave in 2015. Only frail 50-year or older adults (Frailty Index with a cut-off value of 0.21 or higher, was used) were considered for this analysis (n = 1298). A survival analysis was performed with Kaplan-Meier curves and Cox regression models (unadjusted and adjusted for confounding). Socio-demographic, health risks, physical activity and comorbidities were variables used for adjusting the multivariate models. RESULTS:From the total sample of 1298 older adults, 32.5% (n = 422) died during follow-up. The highest hazard ratio in the adjusted model was for calf circumference 1.31 (95% confidence interval 1.02-1.69, p = 0.034). Other measurements were not significant. CONCLUSIONS:Anthropometric measurements have different significance in frail older adults, and these differences could have implications on adverse outcomes. Calf circumference has a potential value in predicting negative health outcomes.
| S-EPMC6109418 | biostudies-literature
Project description:Background: Frailty, a state of increased vulnerability, could play a role in the progression of vascular dementia. We aim to describe the changes in cerebrovascular reactivity of older adults with frailty and vascular-type mild cognitive impairment (MCIv). Methods: This was a cross-sectional study. A comprehensive geriatric assessment, neuropsychological evaluation, and transcranial Doppler ultrasound (TCD) was performed on 180 participants who were allocated into four groups: healthy (n = 74), frail (n = 40), MCIv (n = 35), and mixed (frail + MCIv) (n = 31). ANOVA and Kruskal-Wallis tests were used for the analysis of continuous variables with and without normal distribution. Multinomial logistic regression was constructed to identify associated covariates. Results: Subjects in the mixed group, compared to healthy group, were older (75.0 ± 5.9 vs 70.3 ± 5.9 years; p < 0.001), showed lower education (9.3 ± 6.4 vs 12.2 ± 4.0 years; p = 0.054), greater frequency of diabetes (42% vs 12%; p = 0.005), worse cognitive performance (z = -0.81 ± 0.94), and reduced left medial-cerebral artery cerebrovascular reactivity (0.43 ± 0.42 cm/s). The mixed group was associated with age (odds ratio (OR) 1.16, 95% Confidence Interval (CI) = 1.06-1.27; p < 0.001), diabetes (OR 6.28, 1.81-21.84; p = 0.004), and Geriatric Depression Scale (GDS) score (OR 1.34, 95% CI = 1.09-1.67; p = 0.007). Conclusions: Frailty among older adults was associated with worse cognitive performance, diabetes, and decreased cerebral blood flow.
| S-EPMC6770260 | biostudies-other
Project description:Frailty is common in older adults with fractures. Osteoporosis medications reduce subsequent fracture, but limited data exist on medication efficacy in frail individuals. Our objective was to determine whether medications reduce the risk of subsequent fracture in frail, older adults. A retrospective cohort of Medicare fee-for-service beneficiaries was conducted (2014-2016). We included adults aged ≥65 years who were hospitalized with fractures without osteoporosis treatment. Pre-fracture frailty was defined using claims-based frailty index (≥0.2 = frail). Exposure to any osteoporosis treatment (oral or intravenous bisphosphonates, denosumab, and teriparatide) was ascertained using Part B and D claims and categorized according to the cumulative duration of exposure: none, 1-90 days, and >90 days. Subsequent fractures were ascertained from Part A or B claims. Cause-specific hazard models with time-varying exposure were fit to examine the association between treatment and fracture outcomes, controlling for relevant covariates. Among 29,904 patients hospitalized with fractures, 15,345 (51.3%) were frail, and 2148 (7.2%) received osteoporosis treatment (median treatment duration 183.0 days). Patients who received treatment were younger (80.2 versus 82.2 years), female (86.5% versus 73.0%), and less frail (0.20 versus 0.22) than patients without treatment. During follow-up, 5079 (17.0%) patients experienced a subsequent fracture. Treatment with osteoporosis medications for >90 days compared with no treatment reduced the risk of fracture (hazard ratio [HR] = 0.82; 95% confidence interval [CI] 0.68-1.00) overall. Results were similar in frail (HR = 0.85; 95% CI 0.65-1.12) and non-frail (HR = 0.80; 95% CI 0.61-1.04) patients but not significant. In conclusion, osteoporosis treatment >90 days was associated with similar trends in reduced risk of subsequent fracture in frail and non-frail persons. Treatment rates were very low, particularly among the frail. When weighing treatment options in frail older adults with hospitalized fractures, clinicians should be aware that drug therapy does not appear to lose its efficacy. © 2022 American Society for Bone and Mineral Research (ASBMR).
| S-EPMC9712267 | biostudies-literature
Project description:BACKGROUND:Physical frailty, characterized by reduced physiologic complexity and ability to cope with stressors, is closely associated with cognitive impairment, which increases the risk of poor clinical outcomes. To better capture the association between frailty and cognitive impairment, a new construct, cognitive frailty, has been proposed. Cognitive frailty is a clinical condition characterized by the simultaneous presence of physical frailty and cognitive impairment. There is little evidence on the relationship between physical frailty and cognition, as well as cognitive frailty, in Chinese older adults. We aimed to elucidate whether physical frailty is associated with cognitive impairment in an older Chinese population. METHODS:Data were obtained from the China Comprehensive Geriatric Assessment Study. The sample comprised 3202 community-dwelling adults, aged 60 years and older, from seven Chinese cities. Physical frailty was assessed using a modified, four-item version of the Fried criteria, according to frailty phenotype. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). RESULTS:The prevalence of physical frailty, prefrailty, cognitive impairment, and cognitive frailty was 9.9, 33.9, 7.5, and 2.3%, respectively (weighted: 8.8, 33.8, 6.5, and 2.0%). The prevalence of the combination of prefrail/frail and cognitive impairment was 5.1% (weighted 4.5%). Frail participants performed worse on global cognition and all cognitive domains than robust and prefrail participants. The MMSE total score was positively correlated with walking speed and negatively correlated with age and frailty. A multivariate logistic regression revealed that after adjusting for age, gender, education level, living area, and chronic diseases, frailty, exhaustion, slowness, and inactivity were significantly associated with poor global cognition. CONCLUSIONS:The standard prevalence of physical frailty, prefrailty, cognitive impairment, and cognitive frailty in community-dwelling older adults in China was 8.8, 33.8, 6.5, and 2.0%, respectively. Frailty, exhaustion, slowness, and inactivity were significantly associated with poor global cognition.
| S-EPMC6391822 | biostudies-other
Project description:BackgroundFrailty is characterized by a progressive decline in the physiological functions of multiple body systems that lead to a more vulnerable condition, which is prone to the development of various adverse events, such as falls, hospitalization, and mortality. This study aims to determine whether frailty increases mortality compared to pre-frailty and to identify variables associated with a higher risk of mortality.MaterialsTwo cohorts, frail and pre-frail subjects, are evaluated according to the Fried phenotype. A complete examination of frailty, cognitive status, comorbidities and pharmacology was carried out at hospital admission and was extracted through electronic health record (EHR). Mortality was evaluated from the EHR.MethodsKaplan-Meier estimates of survival probability functions were calculated at two years censoring time for frail and pre-frail cohorts. The log-rank test assessed significant differences between survival probability functions. Significant variables for frailty (p < 0-05) were extracted by independent sample t-test. Further selection was based on variable significance found in multivariate logistic regression discrimination between frail and pre-frail subjects. Cox regression over univariate t-test-selected variables was calculated to identify variables associated with higher proportional hazard risks (HR) at two years.ResultsFrailty is associated with greater mortality at two years censoring time than pre-frailty (log-rank test, p < 0.0001). Variables with significant (p < 0.05) association with mortality identified in both cohorts (HR 95% (CI in the frail cohort) are male sex (0.44 (0.29-0.66)), age (1.05 (1.01-1.09)), weight (0.98 (0.96-1.00)), and use of proton-pump inhibitors (PPIs) (0.60 (0.41-0.87)). Specific high-risk factors in the frail cohort are readmission at 30 days (0.50 (0.33-0.74)), SPPB sit and stand (0.62 (0.45-0.85)), heart failure (0.67 (0.46-0.98)), use of antiplatelets (1.80 (1.19-2.71)), and quetiapine (0.31 (0.12-0.81)). Specific high-risk factors in the pre-frail cohort are Barthel's score (120 (7.7-1700)), Pfeiffer test (8.4; (2.3-31)), Mini Nutritional Assessment (MNA) (1200 (18-88,000)), constipation (0.025 (0.0027-0.24)), falls (18,000 (150-2,200,000)), deep venous thrombosis (8400 (19-3,700,000)), cerebrovascular disease (0.01 (0.00064-0.16)), diabetes (360 (3.4-39,000)), thyroid disease (0.00099 (0.000012-0.085)), and the use of PPIs (0.062 (0.0072-0.54)), Zolpidem (0.000014 (0.0000000021-0.092)), antidiabetics (0.00015 (0.00000042-0.051)), diuretics (0.0003 (0.000004-0.022)), and opiates (0.000069 (0.00000035-0.013)).ConclusionsFrailty is associated with higher mortality at two years than pre-frailty. Frailty is recognized as a systemic syndrome with many links to older-age comorbidities, which are also found in our study. Polypharmacy is strongly associated with frailty, and several commonly prescribed drugs are strongly associated with increased mortality. It must be considered that frail patients need coordinated attention where the diverse specialist taking care of them jointly examines the interactions between the diversity of treatments prescribed.
| S-EPMC10179017 | biostudies-literature
Project description:BACKGROUND:Bisphosphonates are seldom used in frail, older adults, in part due to lack of direct evidence of efficacy in this population and increasing concerns about safety. OBJECTIVE:We estimated the effects of bisphosphonates on hip fractures, nonvertebral fractures, and severe esophagitis among frail, older adults. DESIGN:Population-based retrospective cohort using 2008 to 2013 linked national Minimum Data Set assessments; Online Survey Certification and Reporting System records; and Medicare claims. SETTING:US nursing homes (NHs). PARTICIPANTS:Long-stay NH residents 65 years and older without recent osteoporosis medication use (N = 24,571). Bisphosphonate initiators were 1:1 propensity score matched to calcitonin initiators (active comparator). MEASUREMENTS:Hospitalized hip fracture, nonvertebral fracture, and esophagitis outcomes were measured using part A claims. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated, controlling for over 100 baseline characteristics. RESULTS:The matched cohort included 5209 new bisphosphonate users and an equal number of calcitonin users (mean age [SD] = 85 [8] years; 87% female; 52% moderate-severe cognitive impairment). Over a mean follow-up of 2.5 (SD = 1.7) years, 568 residents (5.5%) had a hip fracture, 874 (8.4%) had a nonvertebral fracture, and 199 (1.9%) had a hospitalized esophagitis event. Users of bisphosphonates were less likely than calcitonin users to experience hip fracture (HR = 0.83; 95% CI = 0.71-0.98), with an average gain in time without fracture of 28.4 days (95% CI = 6.0-50.8 days). Bisphosphonate and calcitonin users had similar rates of nonvertebral fracture (HR = 0.91; 95% CI = 0.80-1.03) and esophagitis events (HR = 1.11; 95% CI = 0.84-1.47). The effects of bisphosphonates on fractures and esophagitis were generally homogeneous across subgroups, including those defined by age, sex, history of prior fracture, and baseline fracture risk. CONCLUSIONS:Use of bisphosphonates is associated with a meaningful reduction in hip fracture among frail, older adults, but little difference in nonvertebral fracture or severe esophagitis. J Am Geriatr Soc 67:768-776, 2019.
| S-EPMC6705123 | biostudies-literature