A growing body of evidence indicates that time restricted feeding (TRF), a popular form of intermittent fasting, can activate similar biological pathways as caloric restriction, the only intervention ...consistently found to extend healthy lifespan in a variety of species. Thus, TRF may have the potential to also improve function in older adults. Given the challenges many individuals have in following calorie restriction regimens over long-time periods, evaluation of alternative approaches that may produce weight loss and improve function in overweight, older adults is important. Ten overweight, sedentary older adults (≥65 years) at risk for, or with mobility impairments, defined by slow gait speed (<1.0 m/s) participated in this trial. All participants received the intervention and were instructed to fast for approximately 16 h per day over the entire four-week intervention. Outcomes included changes in body weight, waist circumference, cognitive and physical function, health-related quality of life, and adverse events. Adherence levels were high (mean = 84%) based on days goal was met, and mean weight loss was 2.6 kg (
< 0.01). Since body composition was not measured in this study, it is unclear if the observed weight loss was due to loss of fat mass, muscle mass, or the combination of fat and muscle mass. There were no significant changes in other outcomes; however, there were clinically meaningful changes in walking speed and improvements in quality of life, with few reported adverse events. The findings of this pilot study suggest that time restricted feeding is an acceptable and feasible eating pattern for overweight, sedentary older adults to follow.
The identification of cost-effective interventions that improve the health status and prevent disability in old age is one of the most important public health challenges. Regular physical activity is ...the only intervention that has consistently been shown to improve functional health and energy balance and to reduce the risk of cardiovascular disease, stroke, diabetes, several cancers, depression and falls. In advanced age, physical activity is also effective at mitigating sarcopenia, restoring robustness, and preventing/delaying the development of disability. On the other hand, physical inactivity is recognized as one of the leading causes of several chronic degenerative diseases and is also a major contributing factor to sarcopenia and functional disability. This compelling evidence has prompted the World Health Organization to recommend engaging in regular physical activity throughout one’s life course. The present review summarizes the available evidence in support of physical activity as a remedy against physical frailty and sarcopenia. The relevant pathways through which the benefits of physical activity are conveyed are also discussed.
Inhibition of the TOR signalling pathway by genetic or pharmacological intervention extends lifespan in invertebrates, including yeast, nematodes and fruitflies; however, whether inhibition of mTOR ...signalling can extend lifespan in a mammalian species was unknown. Here we report that rapamycin, an inhibitor of the mTOR pathway, extends median and maximal lifespan of both male and female mice when fed beginning at 600 days of age. On the basis of age at 90% mortality, rapamycin led to an increase of 14% for females and 9% for males. The effect was seen at three independent test sites in genetically heterogeneous mice, chosen to avoid genotype-specific effects on disease susceptibility. Disease patterns of rapamycin-treated mice did not differ from those of control mice. In a separate study, rapamycin fed to mice beginning at 270 days of age also increased survival in both males and females, based on an interim analysis conducted near the median survival point. Rapamycin may extend lifespan by postponing death from cancer, by retarding mechanisms of ageing, or both. To our knowledge, these are the first results to demonstrate a role for mTOR signalling in the regulation of mammalian lifespan, as well as pharmacological extension of lifespan in both genders. These findings have implications for further development of interventions targeting mTOR for the treatment and prevention of age-related diseases.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Older adults are a rapidly growing segment of the U.S. population. Mobility problems that lead to further disability can be addressed through physical activity interventions. Quality of life outcome ...results are reported from a large trial of physical activity for sedentary older adults at risk for mobility disability.
Data were from the Lifestyle Interventions and Independence for Elders study. This multisite RCT compared physical activity to health education among 1,635 randomly assigned sedentary older adults at risk for mobility disability in 2010–2011. Measures included demographics; comorbidity; a timed 400-meter walk; the Short Physical Performance Battery; and the Quality of Well-Being Scale (0–1.0 scale). Baseline and long-term follow-up (2.6 years) health-related quality of life data were collected as a secondary outcome. Multivariate linear regression modeling was used to examine covariates of health-related quality of life over time in 2017.
The sample had an overall mean Quality of Well-Being score of 0.613. Both groups declined in quality of life over time, but assignment to the physical activity intervention resulted in a slower decline in health-related quality of life scores (p=0.03). Intervention attendance was associated with higher health-related quality of life for both groups. Baseline characteristics including younger age, fewer comorbid conditions, non-white ethnicity, and faster 400-meter walk times were also associated with higher health-related quality of life over time.
Declining mobility measured by physical performance is associated with lower quality of life in sedentary older adults. Physical activity interventions can slow the decline in quality of life, and targeting specific subgroups may enhance the effects of such interventions.
Abstract Objective In this study, we evaluate the impact of disability and multimorbidity on the risk of all-cause death in a population of frail older persons living in community. Study Design and ...Setting We analyzed data from the Aging and Longevity Study in the Sirente geographic area, a prospective cohort study that collected data on all subjects aged 80 years and older ( n = 364). The main outcome measure was all-cause mortality over 4-year follow-up. Results A total of 150 deaths occurred. Sixty-seven subjects (44.6%) died in the nondisabled group compared with 83 subjects (55.3%) in the disabled group ( P < 0.01). Thirty-nine subjects (31.7%) died among subjects without multimorbidity compared with 111 subjects (46.0%) with two or more diseases ( P < 0.01). When examining the combined effect of multimorbidity and disability, the effect of disability on the risk of death was higher than that of multimorbidity. After adjusting for potential confounders, relative to those without disability and multimorbidity, disabled subjects showed an increased risk of death when multimorbidity was associated (hazard ratio HR = 3.91; 95% confidence interval CI = 1.53–10.00) and in absence of multimorbidity (HR = 2.36; 95% CI = 0.63–8.83). Conclusion Our results show that disability exerts an important influence on mortality, independently of age and other clinical and functional variables.
Summary
Age‐related loss of muscle mass and strength (sarcopenia) leads to a decline in physical function and frailty in the elderly. Among the many proposed underlying causes of sarcopenia, ...mitochondrial dysfunction is inherent in a variety of aged tissues. The intent of this study was to examine the effect of aging on key groups of regulatory proteins involved in mitochondrial biogenesis and how this relates to physical performance in two groups of sedentary elderly participants, classified as high‐ and low‐functioning based on the Short Physical Performance Battery test. Muscle mass was decreased by 38% and 30% in low‐functioning elderly (LFE) participants when compared to young and high‐functioning elderly participants, respectively, and positively correlated to physical performance. Mitochondrial respiration in permeabilized muscle fibers was reduced (41%) in the LFE group when compared to the young, and this was associated with a 30% decline in cytochrome c oxidase activity. Levels of key metabolic regulators, SIRT3 and PGC‐1α, were significantly reduced (50%) in both groups of elderly participants when compared to young. Similarly, the fusion protein OPA1 was lower in muscle from elderly subjects; however, no changes were detected in Mfn2, Drp1 or Fis1 among the groups. In contrast, protein import machinery components Tom22 and cHsp70 were increased in the LFE group when compared to the young. This study suggests that aging in skeletal muscle is associated with impaired mitochondrial function and altered biogenesis pathways and that this may contribute to muscle atrophy and the decline in muscle performance observed in the elderly population.
Understanding the minimal dose of physical activity required to achieve improvement in physical functioning and reductions in disability risk is necessary to inform public health recommendations. To ...examine the effect of physical activity dose on changes in physical functioning and the onset of major mobility disability in The Lifestyle Interventions and Independence for Elders (LIFE) Study. We conducted a multicenter single masked randomized controlled trial that enrolled participants in 2010 and 2011 and followed them for an average of 2.6 years. 1,635 sedentary men and women aged 70-89 years who had functional limitations were randomized to a structured moderate intensity walking, resistance, and flexibility physical activity program or a health education program. Physical activity dose was assessed by 7-day accelerometry and self-report at baseline and 24 months. Outcomes included the 400 m walk gait speed, the Short Physical Performance Battery (SPPB), assessed at baseline, 6, 12, and 24 months, and onset of major mobility disability (objectively defined by loss of ability to walk 400 m in 15 min). When the physical activity arm or the entire sample were stratified by change in physical activity from baseline to 24 months, there was a dose-dependent increase in the change in gait speed and SPPB from baseline at 6, 12, and 24 months. In addition, the magnitude of change in physical activity over 24 months was related to the reduction in the onset of major mobility disability (overall P < 0.001) (highest versus the lowest quartile of physical activity change HR 0.23 ((95% CI:0.10-0.52) P = 0.001) in the physical activity arm. We observed a dose-dependent effect of objectively monitored physical activity on physical functioning and onset of major mobility disability. Relatively small increases (> 48 minutes per week) in regular physical activity participation had significant and clinically meaningful effects on these outcomes.
ClinicalsTrials.gov NCT00116194.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
Advances in computational algorithms and the availability of large datasets with clinically relevant characteristics provide an opportunity to develop machine learning prediction ...models to aid in diagnosis, prognosis, and treatment of older adults. Some studies have employed machine learning methods for prediction modeling, but skepticism of these methods remains due to lack of reproducibility and difficulty in understanding the complex algorithms that underlie models. We aim to provide an overview of two common machine learning methods: decision tree and random forest. We focus on these methods because they provide a high degree of interpretability.
Method
We discuss the underlying algorithms of decision tree and random forest methods and present a tutorial for developing prediction models for serious fall injury using data from the Lifestyle Interventions and Independence for Elders (LIFE) study.
Results
Decision tree is a machine learning method that produces a model resembling a flow chart. Random forest consists of a collection of many decision trees whose results are aggregated. In the tutorial example, we discuss evaluation metrics and interpretation for these models. Illustrated using data from the LIFE study, prediction models for serious fall injury were moderate at best (area under the receiver operating curve of 0.54 for decision tree and 0.66 for random forest).
Conclusions
Machine learning methods offer an alternative to traditional approaches for modeling outcomes in aging, but their use should be justified and output should be carefully described. Models should be assessed by clinical experts to ensure compatibility with clinical practice.
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