Falls are a common, serious threat to the health and self-confidence of the elderly. Assessment of fall risk is an important aspect of effective fall prevention programs.
In order to test whether it ...is possible to outperform current prognostic tools for falls, we analyzed 1010 variables pertaining to mobility collected from 976 elderly subjects (InCHIANTI study). We trained and validated a data-driven model that issues probabilistic predictions about future falls. We benchmarked the model against other fall risk indicators: history of falls, gait speed, Short Physical Performance Battery (Guralnik et al. 1994), and the literature-based fall risk assessment tool FRAT-up (Cattelani et al. 2015). Parsimony in the number of variables included in a tool is often considered a proxy for ease of administration. We studied how constraints on the number of variables affect predictive accuracy.
The proposed model and FRAT-up both attained the same discriminative ability; the area under the Receiver Operating Characteristic (ROC) curve (AUC) for multiple falls was 0.71. They outperformed the other risk scores, which reported AUCs for multiple falls between 0.64 and 0.65. Thus, it appears that both data-driven and literature-based approaches are better at estimating fall risk than commonly used fall risk indicators. The accuracy-parsimony analysis revealed that tools with a small number of predictors (~1-5) were suboptimal. Increasing the number of variables improved the predictive accuracy, reaching a plateau at ~20-30, which we can consider as the best trade-off between accuracy and parsimony. Obtaining the values of these ~20-30 variables does not compromise usability, since they are usually available in comprehensive geriatric assessments.
Comparing transcript levels between healthy and diseased individuals allows the identification of differentially expressed genes, which may be causes, consequences or mere correlates of the disease ...under scrutiny. We propose a method to decompose the observational correlation between gene expression and phenotypes driven by confounders, forward- and reverse causal effects. The bi-directional causal effects between gene expression and complex traits are obtained by Mendelian Randomization integrating summary-level data from GWAS and whole-blood eQTLs. Applying this approach to complex traits reveals that forward effects have negligible contribution. For example, BMI- and triglycerides-gene expression correlation coefficients robustly correlate with trait-to-expression causal effects (r
= 0.11, P
= 2.0 × 10
and r
= 0.13, P
= 1.1 × 10
), but not detectably with expression-to-trait effects. Our results demonstrate that studies comparing the transcriptome of diseased and healthy subjects are more prone to reveal disease-induced gene expression changes rather than disease causing ones.
Although low alanine aminotransferase (ALT) levels have been associated with poor outcomes in the elderly population, the determinants subtending this association have been poorly explored. To gain ...insight into this topic, we analyzed data from a prospective population-based database (InCHIANTI study) in which frailty, disability, sarcopenia, and pyridoxine levels were systematically assessed.
Data are from 765 participants aged more than 65 years (mean age 75.3 years, women 61.8%), without chronic liver disease, malignancies, or alcohol abuse. Frailty was defined according to Fried criteria, sarcopenia through peripheral Quantitative-Computed-Tomography (lowest gender-specific tertile of the residuals of a linear regression of muscle mass from height and fat mass), and disability as self-reported need for help in at least one basic daily living activity. Associations of ALT with overall and cardiovascular mortality were assessed by Cox-models with time-dependent covariates.
ALT activity was inversely associated with frailty, sarcopenia, disability, and pyridoxine deficiency; however, higher ALT was confirmed to be protective with respect of overall and cardiovascular mortality even in multiple-adjusted models including all these covariates (overall: hazard ratio HR 0.98 0.96-1, p = .02; cardiovascular: 0.94 0.9-0.98, p < .01). The association between ALT activity and mortality was nonlinear (J-shaped), and subjects in the lower quintiles of ALT levels showed a sharply increased overall and cardiovascular mortality.
These results suggest that reduced ALT levels in older individuals can be considered as a marker of frailty, disability, and sarcopenia, and as an independent predictor of adverse outcomes. The possible relationship between reduced ALT and impaired hepatic metabolic functions should be explored.
Older people with type 2 diabetes are at high risk of mobility disability. We investigated the association of diabetes with lower-limb muscle mass and muscle quality to verify whether ...diabetes-related muscle impairments mediate the association between diabetes and low walking speed.
We performed a cross-sectional analysis of 835 participants (65 years old and older) enrolled in the InCHIANTI (Invecchiare in Chianti, aging in the Chianti area) population-based study. Total, muscular, and fat cross-sectional areas of the calf and relative muscle density were measured using peripheral quantitative computerized tomography. Indicators of muscle performance included knee-extension torque, ankle plantar flexion and dorsiflexion strength, lower-extremity muscle power, and ankle muscle quality (ratio of ankle strength to the muscle area kilograms per centimeters squared). Gait performance was assessed by 4- and 400-m walking speed. Diabetes was ascertained by standard American Diabetes Association criteria.
Prevalence of diabetes was 11.4%. After adjustment for age and sex, participants with diabetes had lower muscle density, knee and ankle strength, and muscle power and worse muscle quality (all P < 0.05). Diabetic participants were also slower on both 4-m (β: -0.115 ± 0.024 m/s, P < 0.001) and 400-m (β:-0.053 ± 0.023 m/s, P < 0.05) walking tests. In multivariable linear regression models, lower-limb muscle characteristics accounted for 24.3 and 15.1% of walking speed difference comparing diabetic and nondiabetic subjects in the 4- and 400-m walks, respectively.
In older persons, diabetes is associated with reduced muscle strength and worse muscle quality. These impairments are important contributors of walking limitations related to diabetes.
Menopause accelerates biological aging Levine, Morgan E.; Lu, Ake T.; Chen, Brian H. ...
Proceedings of the National Academy of Sciences - PNAS,
08/2016, Letnik:
113, Številka:
33
Journal Article
Recenzirano
Odprti dostop
Although epigenetic processes have been linked to aging and disease in other systems, it is not yet known whether they relate to reproductive aging. Recently, we developed a highly accurate ...epigenetic biomarker of age (known as the “epigenetic clock”), which is based on DNA methylation levels. Here we carry out an epigenetic clock analysis of blood, saliva, and buccal epithelium using data from four large studies: the Women’s Health Initiative (n = 1,864); Invecchiare nel Chianti (n = 200); Parkinson’s disease, Environment, and Genes (n = 256); and the United Kingdom Medical Research Council National Survey of Health and Development (n = 790). We find that increased epigenetic age acceleration in blood is significantly associated with earlier menopause (P = 0.00091), bilateral oophorectomy (P = 0.0018), and a longer time since menopause (P = 0.017). Conversely, epigenetic age acceleration in buccal epithelium and saliva do not relate to age at menopause; however, a higher epigenetic age in saliva is exhibited in women who undergo bilateral oophorectomy (P = 0.0079), while a lower epigenetic age in buccal epithelium was found for women who underwent menopausal hormone therapy (P = 0.00078). Using genetic data, we find evidence of coheritability between age at menopause and epigenetic age acceleration in blood. Using Mendelian randomization analysis, we find that two SNPs that are highly associated with age at menopause exhibit a significant association with epigenetic age acceleration. Overall, our Mendelian randomization approach and other lines of evidence suggest that menopause accelerates epigenetic aging of blood, but mechanistic studies will be needed to dissect cause-and-effect relationships further.
Sarcopenia is associated with increased risk of adverse outcomes in older people. Aim of the study was to explore the predictive value of the European Working Group on Sarcopenia in Older People ...(EWGSOP) diagnostic algorithm in terms of disability, hospitalization, and mortality and analyze the specific role of grip strength and walking speed as diagnostic criteria for sarcopenia.
Longitudinal analysis of 538 participants enrolled in the InCHIANTI study. Sarcopenia was defined as having low muscle mass plus low grip strength or low gait speed (EWGSOP criteria). Muscle mass was assessed using bioimpedance analysis. Cox proportional and logistic regression models were used to assess risk of death, hospitalization, and disability for sarcopenic people and to investigate the individual contributions of grip strength and walking speed to the predictive value of the EWGSOP's algorithm.
Prevalence of EWGSOP-defined sarcopenia at baseline was 10.2%. After adjusting for potential confounders, sarcopenia was associated with disability (odds ratio 3.15; 95% confidence interval CI 1.41-7.05), hospitalization (hazard ratio HR 1.57; 95% CI 1.03-2.41), and mortality (HR 1.88; 95% CI 0.91-3.91). The association between an alternative sarcopenic phenotype, defined only by the presence of low muscle mass and low grip strength, and both disability and mortality were similar to the association with the phenotypes defined by low muscle mass and low walking speed or by the EWGSOP algorithm.
The EWGSOP's phenotype is a good predictor of incident disability, hospitalization and death. Assessment of only muscle weakness, in addition to low muscle mass, provided similar predictive value as compared to the original algorithm.
Although turning has been reported as one of the leading activities performed during a fall, and falls during turning result in 8-times more hip fractures than falls during linear gait, the quantity ...and quality of turns resulting in falls remain unknown since turns are rarely assessed during activities of daily living. 160 community-dwelling older adults were monitored for one week using smartphone technology. Turn measures and activity rates were quantified. Fall incidence within 12 months from continuous monitoring defined fall status, with 7/153 prospective fallers/non-fallers. Based on the analysis of 718,582 turns, prospective fallers turned less frequently, took longer to turn, and were less consistent in turn angle (p = 0.007, 0.025, and 0.038, respectively). Prospective fallers also walked slower and spent less time walking and turning and more time engaged in sedentary behavior (p = 0.043, 0.012, and 0.015, respectively). Individuals experiencing decline in the control of gait and/or turning may attempt to reduce their risk of falling by limiting their exposure and implementing cautionary movement strategies while turning. Since there was no difference in the overall active rate between prospective fallers and non-fallers, impaired gait and turning ability, specifically, may attribute to elevated fall risk within this cohort.
Behavioral and lifestyle factors have been shown to relate to a number of health-related outcomes, yet there is a need for studies that examine their relationship to molecular aging rates. Toward ...this end, we use recent epigenetic biomarkers of age that have previously been shown to predict all-cause mortality, chronic conditions, and age-related functional decline. We analyze cross-sectional data from 4,173 postmenopausal female participants from the Women's Health Initiative, as well as 402 male and female participants from the Italian cohort study, Invecchiare nel Chianti.Extrinsic epigenetic age acceleration (EEAA) exhibits significant associations with fish intake (p=0.02), moderate alcohol consumption (p=0.01), education (p=3x10
), BMI (p=0.01), and blood carotenoid levels (p=1x10
)-an indicator of fruit and vegetable consumption, whereas intrinsic epigenetic age acceleration (IEAA) is associated with poultry intake (p=0.03) and BMI (p=0.05). Both EEAA and IEAA were also found to relate to indicators of metabolic syndrome, which appear to mediate their associations with BMI. Metformin-the first-line medication for the treatment of type 2 diabetes-does not delay epigenetic aging in this observational study. Finally, longitudinal data suggests that an increase in BMI is associated with increase in both EEAA and IEAA.Overall, the epigenetic age analysis of blood confirms the conventional wisdom regarding the benefits of eating a high plant diet with lean meats, moderate alcohol consumption, physical activity, and education, as well as the health risks of obesity and metabolic syndrome.
Older age is a strong shared risk factor for many chronic diseases, and there is increasing interest in identifying aging biomarkers. Here, a proteomic analysis of 1301 plasma proteins was conducted ...in 997 individuals between 21 and 102 years of age. We identified 651 proteins associated with age (506 over-represented, 145 underrepresented with age). Mediation analysis suggested a role for partial
-epigenetic control of protein expression with age. Of the age-associated proteins, 33.5% and 45.3%, were associated with mortality and multimorbidity, respectively. There was enrichment of proteins associated with inflammation and extracellular matrix as well as senescence-associated secretory proteins. A 76-protein proteomic age signature predicted accumulation of chronic diseases and all-cause mortality. These data support the use of proteomic biomarkers to monitor aging trajectories and to identify individuals at higher risk of disease to be targeted for in depth diagnostic procedures and early interventions.
Abstract
Background
A universal definition of sarcopenia is still lacking. Since the European criteria have been recently revised, we aimed at studying prevalence of low muscle strength (LMS) and low ...muscle mass (LMM), as defined according to the European Working Group of Sarcopenia in Older People (EWGSOP) 2 and 1 definitions, and their individual contribution toward mortality and incident mobility disability in a cohort of community-dwelling older people.
Methods
Longitudinal analysis of 535 participants of the InCHIANTI study. LMS and LMM were defined according to the criteria indicated in the EWGSOP2 and 1. Cox and log-binomial regressions were used to examine association with mortality and 3-year mobility disability (inability to walk 400 m).
Results
We observed a lower prevalence of the combination LMM/LMS according to EWGSOP2 compared to EWGSOP1 (3.2% vs 6.2%). Using the new criteria, all sarcopenia components were associated with mortality, although the hazard ratio HR for the group LMM/LMS was no longer significant after adjustment for confounders (LMM: HR 2.69, 95% confidence interval CI 1.04–6.94; LMS: HR 3.18, 95% CI 1.44–7.01; LMM/LMS: HR 2.95, 95% CI 0.86–10.16). Using EWGSOP1, LMS alone was independently associated with mortality (HR 4.43, 95% CI 1.85–10.57). None of the sarcopenia components conferred a higher risk of mobility disability.
Conclusions
The EWGSOP2 algorithm leads to a reduction in the estimated prevalence of sarcopenia defined as combination of LMM/LMS. The finding that, independent of the adopted criteria, people with LMS and normal mass have a higher mortality risk compared to robust individuals, confirms that evaluation of muscle strength has a central role for prognosis evaluation.
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