Suchergebnisse

Abstract
Aging is characterized by a progressive loss of cellular functions that increase the risk of developing chronic diseases, vascular dysfunction, and neurodegenerative conditions. The field of geroscience has identified cellular and molecular hallmarks of aging that may serve as targets for future interventions to reduce the risk of age-related disease and disability. These hallmarks include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. Several studies show that exercise may favorably affect these processes and thereby have antiaging properties. The primary mechanisms through which exercise confers protective benefits in the brain are still incompletely understood. To better understand these effects and leverage them to help promote brain health, we present current findings supporting the notion that adaptive responses to exercise play a pivotal role in mitigating the hallmarks of aging and their effects on the aging cerebrovasculature, and ultimately contribute to the maintenance of brain function across the healthspan.

Abstract

Background
Although frailty is associated with a range of adverse health outcomes, its association with the risk of hospital-treated infections is uncertain.


Methods
A total of 416 220 participants from the UK Biobank were included in this prospective cohort study. Fried phenotype was adopted to evaluate frailty, which included 5 aspects (gait speed, physical activity, grip strength, exhaustion, and weight). More than 800 infectious diseases were identified based on electronic health records. Cox proportional models were used to estimate the associations.


Results
During a median 12.3 years (interquartile range 11.4–13.2) of follow-up (4 747 345 person-years), there occurred 77 988 (18.7%) hospital-treated infections cases. In the fully adjusted model, compared with participants with nonfrail, the hazard ratios (HRs) (95% confidence intervals [CIs]) of those with prefrail and frail for overall hospital-treated infections were 1.22 (1.20, 1.24) and 1.78 (1.72–1.84), respectively. The attributable risk proportion of prefrail and frail were 18.03% and 43.82%. Similarly, compared to those without frailty, the HRs (95% CIs) of those with frailty for bacterial infections were 1.76 (1.70–1.83), for viral infections were 1.62 (1.44–1.82), and for fungal infections were 1.75 (1.47–2.08). No association was found between frailty and parasitic infections (HR: 1.17; 95% CI: 0.62–2.20).


Conclusions
Frailty was significantly associated with a higher risk of hospital-treated infections, except for parasitic infections. Studies evaluating the effectiveness of implementing frailty assessments are needed to confirm our results.

Abstract

Background
Circulating levels of n-3 polyunsaturated fatty acids (PUFAs) have been associated with frailty among Koreans (a population with a high intake of fish), but whether this association exists in Western populations with low fish intake is unknown. The present study examined the hypothesis that the prevalence of frailty was inversely associated with plasma levels of n-3 PUFAs, with the intake of oily fish, and with fish oil supplementation in older adults in the United Kingdom.


Methods
UK Biobank including 79 330 adults aged ≥65 years with dietary data, and 18 802 participants with plasma fatty acid data were used. Frailty was defined using the Cardiovascular Health Study index, plasma levels of n-3 PUFAs were measured by nuclear magnetic resonance, and intake of oily fish and/or fish oil supplements was collected via food frequency questionnaire.


Results
Frailty prevalence was inversely associated with n-3 PUFA levels [odds ratios (OR) per SD: 0.86, 95% confidence interval (CI) 0.79–0.94; p < .001], with oily fish intake (never vs ≥2 servings per week; OR 0.59, 95% CI 0.52–0.68, p < .001), and with the use of fish oil supplements (OR 0.72; 95% CI 0.66–0.78; p < .001) after adjusting for confounding factors. All 3 exposures were also associated with each frailty criterion, particularly low physical activity and walking pace.


Conclusions
Inverse associations between plasma n-3 PUFA levels and measures of frailty suggest that higher intakes of oily fish or the use of fish oil supplements may help prevent frailty in older adults in the United Kingdom.

Abstract

Background
High-dimensional propensity scoring (HDPS) is a method for empirically identifying potential confounders within large healthcare databases such as administrative claims data. However, this method has not yet been applied to large national health surveys such as the National Health and Aging Trends Study (NHATS), an ongoing nationally representative survey of older adults in the United States and important resource in gerontology research.


Methods
In this Research Practice article, we present an overview of HDPS and describe the specific data transformation steps and analytic considerations needed to apply it to national health surveys. We applied HDPS within NHATS to investigate the association between self-reported visual difficulty and incident dementia, comparing HDPS to conventional confounder selection methods.


Results
Among 7 207 dementia-free NHATS Wave 1 respondents, 528 (7.3%) had self-reported visual difficulty. In an unadjusted discrete time proportional hazards model accounting for the complex survey design of NHATS, self-reported visual difficulty was strongly associated with incident dementia (odds ratio [OR] 2.34, 95% confidence interval [CI]: 1.95–2.81). After adjustment for standard investigator-selected covariates via inverse probability weighting, the magnitude of this association decreased, but evidence of an association remained (OR 1.44, 95% CI: 1.11–1.85). Adding 75 HDPS-prioritized variables to the investigator-selected propensity score model resulted in further attenuation of the association between visual impairment and dementia (OR 0.94, 95% CI: 0.70–1.23).


Conclusions
HDPS can be successfully applied to national health surveys such as NHATS and may improve confounder adjustment. We hope developing this framework will encourage future consideration of HDPS in this setting.

Abstract
Physical activity and exercise training exert multiple and varied beneficial effects on a wide array of human tissues, making them therapeutic modalities that can prevent and treat age-related decline in physical function. The Molecular Transducers of Physical Activity Consortium is currently working to elucidate the molecular mechanisms underlying how physical activity improves and preserves health. Exercise training, especially when task specific, is an effective intervention for improving skeletal muscle performance and physical function in everyday activities. As seen elsewhere in this supplement, its adjunctive use with pro-myogenic pharmaceuticals may prove to be synergistic in effect. Behavioral strategies aiming to promote exercise participation and sustain adherence are being considered as additional adjuncts to further improve physical function in comprehensive, multicomponent interventions. One application of this combined strategy may be to target multimodal pro-myogenic therapies in prehabilitation to optimize physical preoperative health to enhance functional recovery postsurgery. We summarize here recent progress on biological mechanisms of exercise training, behavioral approaches to exercise participation, and the role task-specific exercise plays in synergy with pharmacologic therapies with a particular focus on older adults. Physical activity and exercise training in multiple settings should serve as the baseline standard of care around which other therapeutic interventions should be considered when the goal is restoring or increasing physical function.

Abstract

Background
Vulnerable populations across the United States are frequently exposed to extreme heat, which is becoming more intense due to a combination of climate change and urban-induced warming. Extreme heat can be particularly detrimental to the health and well-being of older citizens when it is combined with ozone. Although population-based studies have demonstrated associations between ozone, extreme heat, and human health, few studies focused on the role of social and behavioral factors that increase indoor risk and exposure among older adults.


Methods
We conducted a household survey that aimed to understand how older adults are affected by extreme heat and ozone pollution inside and outside of their homes across Houston, Phoenix, and Los Angeles. We examine contributing factors to the risk of self-reported health effects using a generalized linear mixed-effects regression model of telephone survey data of 909 older adults in 2017.


Results
We found an increased occurrence of self-reported symptoms for extreme heat with preexisting respiratory health conditions and a lack of air conditioning access; self-reported ozone symptoms were more likely with preexisting respiratory health conditions. The risk of heat-related symptoms was slightly higher in Los Angeles than Houston and Phoenix. We found several demographic, housing, and behavioral characteristics that influenced the risk of heat- and ozone-related symptoms.


Conclusions
The increased risk among older adults based on specific social and behavioral factors identified in this study can inform public health policy and help cities tailor their heat and ozone response plans to the specific needs of this vulnerable population.

Abstract

Background
The relationship of claims-based frailty index (CFI), a validated measure to identify frail individuals using Medicare data, and frailty measures used in clinical practice has not yet been fully explored.


Methods
We identified community-dwelling participants of the 2015 National Health and Aging Trends Study (NHATS) whose CFI scores could be calculated using linked Medicare claims. We calculated 9 commonly used clinical frailty measures from their NHATS in-person examination: Study of Osteoporotic Fracture Index (SOF), FRAIL Scale, Frailty Phenotype, Clinical Frailty Scale (CFS), Vulnerable Elder Survey-13 (VES-13), Tilburg Frailty Indicator (TFI), Groningen Frailty Indicator (GFI), Edmonton Frail Scale (EFS), and 40-item Frailty Index (FI). Using equipercentile method, CFI scores were linked to clinical frailty measures. C-statistics and test characteristics of CFI to identify frailty as defined by each clinical frailty measure were calculated.


Results
Of the 3 963 older adults, 44.5% were ≥75 years, 59.4% were female, and 82.3% were non-Hispanic White. A CFI of 0.25 was equipercentile to the following clinical frailty measure scores: SOF 1.4, FRAIL 1.8, Phenotype 1.8, CFS 5.4, VES-13 5.7, TFI 4.6, GFI 5.0, EFS 6.0, and FI 0.26. The C-statistics of using CFI to identify frailty as defined by each clinical measure were ≥0.70, except for CFS and VES-13. The optimal CFI cutpoints to identify frailty per clinical frailty measure ranged from 0.212 to 0.242, with sensitivity and specificity of 0.37–0.83 and 0.66–0.84, respectively.


Conclusions
Understanding the relationship of CFI and commonly used clinical frailty measures can enhance the interpretability and potential utility of CFI.

Abstract

Background
Age is the greatest risk factor for lower urinary tract symptoms attributed to benign prostatic hyperplasia (LUTS/BPH). Although LUTS/BPH can be managed with pharmacotherapy, treatment failure has been putatively attributed to numerous pathological features of BPH (eg, prostatic fibrosis, inflammation). Mitochondrial dysfunction is a hallmark of aging; however, its impact on the pathological features of BPH remains unknown.


Methods
Publicly available gene array data were analyzed. Immunohistochemistry examined mitochondrial proteins in the human prostate. The effect of complex I inhibition (rotenone) on a prostatic cell line was examined using quantitative polymerase chain reaction, immunocytochemistry, and Seahorse assays. Oleic acid (OA) was tested as a bypass of complex I inhibition. Aged mice were treated with OA to examine its effects on urinary dysfunction. Voiding was assessed longitudinally, and a critical complex I protein measured.


Results
Mitochondrial function and fibrosis genes were altered in BPH. Essential mitochondrial proteins (ie, voltage-dependent anion channels 1 and 2, PTEN-induced kinase 1, and NADH dehydrogenase [ubiquinone] iron–sulfur protein 3, mitochondrial [NDUFS3]) were significantly (p < .05) decreased in BPH. Complex I inhibition in cultured cells resulted in decreased respiration, altered NDUFS3 expression, increased collagen deposition, and gene expression. OA ameliorated these effects. OA-treated aged mice had significantly (p < .05) improved voiding function and higher prostatic NDUFS3 expression.


Conclusions
Complex I dysfunction is a potential contributor to fibrosis and lower urinary tract dysfunction in aged mice. OA partially bypasses complex I inhibition and therefore should be further investigated as a mitochondrial modulator for treatment of LUTS/BPH. Hypotheses generated in this investigation offer a heretofore unexplored cellular target of interest for the management of LUTS/BPH.

Abstract

Background
The hemodynamics of prefrontal cortex (PFC) oxygenation are regulated by numerous processes operating over multiple temporal scales, producing complex patterns in its output fluctuations. Age may alter this multiscale regulation of PFC oxygenation, leading to diminished physiologic complexity of this important regulatory process. We aimed to characterize the effects of age on such complexity and its relationship to performance of an executive n-back task.


Methods
Twenty-four younger (aged 28 ± 3 years) and 27 older (aged 78 ± 6 years) adults completed this study. Continuous oxygenation (HbO2) and deoxygenation (HHb) signals of PFC were recorded using functional near-infrared spectroscopy (fNIRS) while participants stood and watched a blank screen (blank), clicked a mouse when an X appeared (IdX), or when a letter was repeated from "2-back" in a sequence shown on a screen (2-back). We used multiscale entropy to quantify the HbO2 and HHb complexity of fNIRS signals.


Results
Older adults exhibited lower HbO2 and HHb complexity compared to younger adults, regardless of task (p = .0005–.002). Both groups exhibited greater complexity during the IdX and 2-back than blank task (p = .02–.04). Across all participants, those with greater HbO2 and/or HHb complexity during the blank task exhibited faster IdX and 2-back reaction time (β = −0.56 to −0.6, p = .009–.02). Those demonstrating greater increase in HbO2 and/or HHb complexity from IdX to 2-back task had lower percent increase in reaction time from IdX to 2-back task (β = −0.41 to −0.37, p = .005–.01).


Conclusions
The complexity of fNIRS-measured PFC oxygenation fluctuations may capture the influence of aging on the regulation of prefrontal hemodynamics involved in executive-function-based task performance.

Abstract

Background
The rapidly growing field of multimorbidity research demonstrates that changes in multimorbidity in mid- and late-life have far reaching effects on important person-centered outcomes, such as health-related quality of life. However, there are few organizing frameworks and comparatively little work weighing the merits and limitations of various quantitative methods applied to the longitudinal study of multimorbidity.


Methods
We identify and discuss methods aligned to specific research objectives with the goals of (i) establishing a common language for assessing longitudinal changes in multimorbidity, (ii) illuminating gaps in our knowledge regarding multimorbidity progression and critical periods of change, and (iii) informing research to identify groups that experience different rates and divergent etiological pathways of disease progression linked to deterioration in important health-related outcomes.


Results
We review practical issues in the measurement of multimorbidity, longitudinal analysis of health-related data, operationalizing change over time, and discuss methods that align with 4 general typologies for research objectives in the longitudinal study of multimorbidity: (i) examine individual change in multimorbidity, (ii) identify subgroups that follow similar trajectories of multimorbidity progression, (iii) understand when, how, and why individuals or groups shift to more advanced stages of multimorbidity, and (iv) examine the coprogression of multimorbidity with key health domains.


Conclusions
This work encourages a systematic approach to the quantitative study of change in multimorbidity and provides a valuable resource for researchers working to measure and minimize the deleterious effects of multimorbidity on aging populations.