Objective
Intermittent fasting (IF) is a term used to describe a variety of eating patterns in which no or few calories are consumed for time periods that can range from 12 hours to several days, on ...a recurring basis. This review is focused on the physiological responses of major organ systems, including the musculoskeletal system, to the onset of the metabolic switch: the point of negative energy balance at which liver glycogen stores are depleted and fatty acids are mobilized (typically beyond 12 hours after cessation of food intake).
Results and Conclusions
Emerging findings suggest that the metabolic switch from glucose to fatty acid‐derived ketones represents an evolutionarily conserved trigger point that shifts metabolism from lipid/cholesterol synthesis and fat storage to mobilization of fat through fatty acid oxidation and fatty acid‐derived ketones, which serve to preserve muscle mass and function. Thus, IF regimens that induce the metabolic switch have the potential to improve body composition in overweight individuals. Moreover, IF regimens also induce the coordinated activation of signaling pathways that optimize physiological function, enhance performance, and slow aging and disease processes. Future randomized controlled IF trials should use biomarkers of the metabolic switch (e.g., plasma ketone levels) as a measure of compliance and of the magnitude of negative energy balance during the fasting period.
White matter hyperintensities are frequent on neuroimaging of older people and are a key feature of cerebral small vessel disease. They are commonly attributed to chronic hypoperfusion, although ...whether low cerebral blood flow is cause or effect is unclear. We systematically reviewed studies that assessed cerebral blood flow in small vessel disease patients, performed meta-analysis and sensitivity analysis of potential confounders. Thirty-eight studies (n = 4006) met the inclusion criteria, including four longitudinal and 34 cross-sectional studies. Most cerebral blood flow data were from grey matter. Twenty-four cross-sectional studies (n = 1161) were meta-analysed, showing that cerebral blood flow was lower in subjects with more white matter hyperintensity, globally and in most grey and white matter regions (e.g. mean global cerebral blood flow: standardised mean difference−0.71, 95% CI −1.12, −0.30). These cerebral blood flow differences were attenuated by excluding studies in dementia or that lacked age-matching. Four longitudinal studies (n = 1079) gave differing results, e.g., more baseline white matter hyperintensity predated falling cerebral blood flow (3.9 years, n = 575); cerebral blood flow was low in regions that developed white matter hyperintensity (1.5 years, n = 40). Cerebral blood flow is lower in subjects with more white matter hyperintensity cross-sectionally, but evidence for falling cerebral blood flow predating increasing white matter hyperintensity is conflicting. Future studies should be longitudinal, obtain more white matter data, use better age-correction and stratify by clinical diagnosis.
Introduction Muscle strength may play a role in cardiometabolic disease. We examined the relationship between hand grip strength and diabetes and hypertension in a sample of healthy weight adults. ...Methods In 2015, we analyzed the National Health and Nutrition Examination Survey 2011–2012 for adults aged ≥20 years with healthy BMIs (between 18.5 and <25) and no history of cardiovascular disease (unweighted n =1,467; weighted n =61,587,139). Hand grip strength was assessed with a dynamometer. Diabetes was based on hemoglobin A1c level and reported diabetes diagnosis. Hypertension was based on measured blood pressure and reported hypertension diagnosis. Results Individuals with undiagnosed diabetes compared with individuals without diabetes had lower grip strength (51.9 vs 69.8, p =0.0001), as did individuals with diagnosed diabetes compared with individuals without diabetes (61.7 vs 69.8, p =0.008). Mean grip strength was lower among individuals with undiagnosed hypertension compared with individuals without hypertension (63.5 vs 71.5, p =0.008) as well as among individuals with diagnosed hypertension compared with those without hypertension (60.8 vs 71.5, p <0.0001). In adjusted analyses controlling for age, sex, race, smoking status, and first-degree relative with disease, mean grip strength was lower for undiagnosed diabetes (β=–10.02, p <0.0001) and diagnosed diabetes (β=–8.21, p =0.03) compared with individuals without diabetes. In adjusted analyses, grip strength was lower among individuals with undiagnosed hypertension (β=–6.6, p =0.004) and diagnosed hypertension (β=–4.27, p =0.04) compared with individuals without hypertension. Conclusions Among healthy weight adults, combined grip strength is lower in individuals with diagnosed and undiagnosed diabetes and hypertension.
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.
Trimethylamine-N-oxide (TMAO) is a gut-derived metabolite associated with cardiovascular disease (CVD). In preclinical and observational studies, resveratrol and exercise training have been suggested ...as potential strategies to reduce the systemic levels of TMAO. However, evidence from experimental studies in humans remains unknown. This project examined the dose-dependent effects of a combined resveratrol intervention with exercise training on circulating TMAO and other related metabolite signatures in older adults with high CVD risk.
Forty-one older adults mean (±SD) age of 72.1 (6.8) years participated in a 12-week supervised center-based, multi-component exercise training intervention 2×/week; 80 min/session and were randomized to one of two resveratrol dosages Low: 500 vs. High:1000 mg/day or a cellulose-based placebo. Serum/plasma were collected at baseline and post-intervention and evaluated for TMAO and associated analytes.
After the 12-week intervention, TMAO concentration increased over time, regardless of treatment mean (±SD) Placebo: 11262 (±3970); Low:13252 (±1193); High: 12661(±3359) AUC; p = 0.04. Each resveratrol dose produced different changes in metabolite signatures. Low dose resveratrol upregulated metabolites associated with bile acids biosynthesis (i.e., glycochenodeoxycholic acid, glycoursodeoxycholic acid, and glycocholic acid). High dose resveratrol modulated metabolites enriched for glycolysis, and pyruvate, propanoate, β-alanine, and tryptophan metabolism. Different communities tightly correlated to TMAO and resveratrol metabolites were associated with the lipid and vascular inflammatory clinical markers |r| > 0.4, p < 0.05.
These findings suggest a distinct dose-dependent adaptation response to resveratrol supplementation on circulating metabolite signatures but not on TMAO among high-risk CVD older adults when combined with an exercise training intervention.
•TMAO is associated with detrimental physiological effects on cardiovascular disease.•Combining resveratrol plus exercise to reduce TMAO's effects remains elusive.•TMAO concentration increased over time, regardless of the combined dose-treatment.•Low dose resveratrol upregulated metabolites associated with bile acids synthesis.•Integrative network analysis showed communities correlated to TMAO and resveratrol.
The independent emergence late in 2020 of the B.1.1.7, B.1.351, and P.1 lineages of SARS-CoV-2 prompted renewed concerns about the evolutionary capacity of this virus to overcome public health ...interventions and rising population immunity. Here, by examining patterns of synonymous and non-synonymous mutations that have accumulated in SARS-CoV-2 genomes since the pandemic began, we find that the emergence of these three “501Y lineages” coincided with a major global shift in the selective forces acting on various SARS-CoV-2 genes. Following their emergence, the adaptive evolution of 501Y lineage viruses has involved repeated selectively favored convergent mutations at 35 genome sites, mutations we refer to as the 501Y meta-signature. The ongoing convergence of viruses in many other lineages on this meta-signature suggests that it includes multiple mutation combinations capable of promoting the persistence of diverse SARS-CoV-2 lineages in the face of mounting host immune recognition.
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•Detected a major global shift in the SARS-CoV-2 selective landscape in late 2020•Identified ongoing convergent evolution between the alpha, beta, and gamma lineages•Defined the mutational meta-signature upon which these lineages are converging
An analysis of synonymous and non-synonymous mutations in SARS-CoV-2 genomes since the inception of the COVID-19 pandemic provides insights into the emergence of a convergent mutational signature in the 501Y lineage (alpha, beta, and gamma variants) that is also likely present in other lineages that impacts host immune recognition.
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.
Consumption of sugar-sweetened beverages may be one of the dietary causes of metabolic disorders, such as obesity. Therefore, substituting sugar with low calorie sweeteners may be an efficacious ...weight management strategy. We tested the effect of preloads containing stevia, aspartame, or sucrose on food intake, satiety, and postprandial glucose and insulin levels. Design: 19 healthy lean (BMI=20.0–24.9) and 12 obese (BMI=30.0–39.9) individuals 18–50 years old completed three separate food test days during which they received preloads containing stevia (290kcal), aspartame (290kcal), or sucrose (493kcal) before the lunch and dinner meal. The preload order was balanced, and food intake (kcal) was directly calculated. Hunger and satiety levels were reported before and after meals, and every hour throughout the afternoon. Participants provided blood samples immediately before and 20min after the lunch preload. Despite the caloric difference in preloads (290kcal vs. 493kcal), participants did not compensate by eating more at their lunch and dinner meals when they consumed stevia and aspartame versus sucrose in preloads (mean differences in food intake over entire day between sucrose and stevia=301kcal, p<.01; aspartame=330kcal, p<.01). Self-reported hunger and satiety levels did not differ by condition. Stevia preloads significantly reduced postprandial glucose levels compared to sucrose preloads (p<.01), and postprandial insulin levels compared to both aspartame and sucrose preloads (p<.05). When consuming stevia and aspartame preloads, participants did not compensate by eating more at either their lunch or dinner meal and reported similar levels of satiety compared to when they consumed the higher calorie sucrose preload.
Obesity and diabetes are known risk factors for the development of physical disability among older adults. With the number of seniors with these conditions rising worldwide, the prevention and ...treatment of physical disability in these persons have become a major public health challenge. Sarcopenia, the progressive loss of muscle mass and strength, has been identified as a common pathway associated with the initial onset and progression of physical disability among older adults. A growing body of evidence suggests that metabolic dysregulation associated with obesity and diabetes accelerates the progression of sarcopenia, and subsequently functional decline in older adults. The focus of this brief review is on the contributions of obesity and diabetes in accelerating sarcopenia and functional decline among older adults. We also briefly discuss the underexplored interaction between obesity and diabetes that may further accelerate sarcopenia and place obese older adults with diabetes at particularly high risk of disability. Finally, we review findings from studies that have specifically tested the efficacy of lifestyle-based interventions in maintaining the functional status of older persons with obesity and/or diabetes.
•Age-related physical disability is an important public health concern.•Obesity and diabetes each independently increase the risk of disability in seniors.•Obese, diabetic older adults appear to be among highest risk for becoming disabled.•Lifestyle-based interventions have shown efficacy for improving physical function.•Questions remain regarding functional decline in obese vs. non-obese diabetics.
Objective
A growing body of evidence has supported the health benefits of extended daily fasting, known as time‐restricted eating (TRE); however, whether the addition of TRE enhances the known ...benefits of calorie restriction (CR) remains unclear.
Methods
PubMed, Scopus, the Cochrane Library, and Google Scholar were searched through April 2023. This systematic review includes randomized controlled trials (RCTs) that compared CR + TRE with CR alone in energy‐matched conditions of at least 8 weeks in duration that assessed changes in body weight and cardiometabolic disease risk factors in adults with overweight and/or obesity.
Results
Seven studies were identified (n = 579). Two studies reported greater weight loss and reductions in diastolic blood pressure with CR + TRE compared with CR alone after 8 to 14 weeks, whereas one study reported greater improvements in triglycerides and glucose tolerance with CR + TRE (3 days/week) compared with CR alone following 26 weeks. One study reported significant increases in homeostatic model assessment of insulin resistance (HOMA‐IR) levels with CR + TRE versus CR alone after 8 weeks. There were no statistically significant differences in any other outcome variable between the two interventions.
Conclusions
The addition of TRE to CR regimens resulted in greater weight loss and improvements in cardiometabolic risk factors in some studies; however, the majority of studies did not find additional benefits.
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