Chronic inflammation represents one of the most consistent biologic features of aging. However, the precise etiology of persistent low-grade increases in inflammation remains unclear. Recent evidence ...suggests that the gut microbiome may play a key role in age-related inflammation. Indeed, several studies have indicated that older adults display an altered composition of the gut microbiota, and early evidence indicates that this dysbiosis is associated with the presence of several key circulating inflammatory analytes. The present review summarizes knowledge on age-related inflammation and discusses how potential relationships with gut dysbiosis may lead to novel treatment strategies in the future."The pattern of disease is an expression of the response of man to his total environment (physical, biological, and social); this response is, therefore, determined by anything that affects man himself or his environment." - Rene Dubos, 1961.
Sarcopenia, the age-related loss of muscle mass and function, imposes a dramatic burden on individuals and society. The development of preventive and therapeutic strategies against sarcopenia is ...therefore perceived as an urgent need by health professionals and has instigated intensive research on the pathophysiology of this syndrome. The pathogenesis of sarcopenia is multifaceted and encompasses lifestyle habits, systemic factors (e.g., chronic inflammation and hormonal alterations), local environment perturbations (e.g., vascular dysfunction), and intramuscular specific processes. In this scenario, derangements in skeletal myocyte mitochondrial function are recognized as major factors contributing to the age-dependent muscle degeneration. In this review, we summarize prominent findings and controversial issues on the contribution of specific mitochondrial processes – including oxidative stress, quality control mechanisms and apoptotic signaling – on the development of sarcopenia. Extramuscular alterations accompanying the aging process with a potential impact on myocyte mitochondrial function are also discussed. We conclude with presenting methodological and safety considerations for the design of clinical trials targeting mitochondrial dysfunction to treat sarcopenia. Special emphasis is placed on the importance of monitoring the effects of an intervention on muscle mitochondrial function and identifying the optimal target population for the trial.
This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.
The gastrointestinal tract contains trillions of microbes (collectively known as the gut microbiota) that play essential roles in host physiology and health. Studies from our group and others have ...demonstrated that exercise independently alters the composition and functional capacity of the gut microbiota. Here, we review what is known about the gut microbiota, how it is studied, and how it is influenced by exercise training and discuss the potential mechanisms and implications for human health and disease.
The Gut Microbiome and Aging Buford, Thomas W
The journals of gerontology. Series A, Biological sciences and medical sciences,
06/2020, Letnik:
75, Številka:
7
Journal Article
Recenzirano
It is now widely recognized that the gut microbiota - the accumulation of micro-organisms that colonize the human intestinal system - play a critical role in the regulation of human health. Indeed, ...it seems that almost daily a new publication links the microbiota and/or the microbiome (the aggregate genetic material of the microbiota) are linked to some new aspect of human health. Given the ubiquitous nature of the gut microbiome in science now, it may be difficult to recall that only a decade ago this field was a fringe scientific interest at best.
Hospital-associated disability (HAD), defined as loss of independence in activities of daily living (ADL) following acute hospitalization, is observed among older adults. The study objective is to ...determine overall prevalence of HAD among older adults hospitalized in acute care, and to assess the impact of study initiation year in moderation of prevalence.
Meta-analysis of data collected from randomized trials, quasi-experimental, and prospective cohort studies. English-language searches to identify included studies were completed February 2018 and updated May 2018 of electronic databases and reference lists of studies and reviews. Included studies were human subjects investigations that measured ADL ≥2 time points before or during and after hospitalization and reported prevalence of ADL decline among older adults.
Acute care hospital units.
Adults aged ≥65 years hospitalized in medical-surgical acute care; total sample size across all included studies was 7375.
Independence in ADL was assessed using the Katz Index of Independence in Activities of Daily Living and Barthel Index of Independence in Activities of Daily Living.
Random effects meta-analysis across included studies identified combined prevalence of HAD as 30% (95% CI 24%, 33%; P < .001). The effect of study initiation year on the prevalence rate was minimal. A large amount of heterogeneity was observed between studies, which may be due in part to nonstandardized measurement of ADL impairment or other methodological differences.
Hospitalization in acute care poses a significant risk to functional independence of older adults, and this risk is unchanged despite shorter lengths of stay. The evidence supports the continued need for hospital-based programs that provide assessment of functional ability and identification of at-risk older adults in order to better treat and prevent HAD.
Highlights • A consensus definition is needed for the multi-faceted construct of “successful aging” to advance the development of strategies that promote independence in an aging population. • Once ...accepted definitions, metrics, and measures to evaluate dimensions of the construct of successful aging are agreed upon, the effectiveness of treatment approaches targeting these outcomes can be better assessed. • A number of health conditions, behavioral factors, and biological mechanisms have been strongly linked to the pathogenesis of functional decline during aging. • Few therapies have been identified to improve functional performance in human aging, and there are currently no FDA-approved medications for the treatment of functional decline in older adults. • Empirically-supported treatments are urgently needed to improve mobility and prevent disability in older adults.
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.
Objective To test whether a long term, structured physical activity program compared with a health education program reduces the risk of serious fall injuries among sedentary older people with ...functional limitations.Design Multicenter, single blinded randomized trial (Lifestyle Interventions and Independence for Elders (LIFE) study).Setting Eight centers across the United States, February 2010 to December 2011.Participants 1635 sedentary adults aged 70-89 years with functional limitations, defined as a short physical performance battery score ≤9, but who were able to walk 400 m.Interventions A permuted block algorithm stratified by field center and sex was used to allocate interventions. Participants were randomized to a structured, moderate intensity physical activity program (n=818) conducted in a center (twice a week) and at home (3-4 times a week) that included aerobic, strength, flexibility, and balance training activities, or to a health education program (n=817) consisting of workshops on topics relevant to older people and upper extremity stretching exercises.Main outcome measures Serious fall injuries, defined as a fall that resulted in a clinical, non-vertebral fracture or that led to a hospital admission for another serious injury, was a prespecified secondary outcome in the LIFE Study. Outcomes were assessed every six months for up to 42 months by staff masked to intervention assignment. All participants were included in the analysis.Results Over a median follow-up of 2.6 years, a serious fall injury was experienced by 75 (9.2%) participants in the physical activity group and 84 (10.3%) in the health education group (hazard ratio 0.90, 95% confidence interval 0.66 to 1.23; P=0.52). These results were consistent across several subgroups, including sex. However, in analyses that were not prespecified, sex specific differences were observed for rates of all serious fall injuries (rate ratio 0.54, 95% confidence interval 0.31 to 0.95 in men; 1.07, 0.75 to 1.53 in women; P=0.043 for interaction), fall related fractures (0.47, 0.25 to 0.86 in men; 1.12, 0.77 to 1.64 in women; P=0.017 for interaction), and fall related hospital admissions (0.41, 0.19 to 0.89 in men; 1.10, 0.65 to 1.88 in women; P=0.039 for interaction).Conclusions In this trial, which was underpowered to detect small, but possibly important reductions in serious fall injuries, a structured physical activity program compared with a health education program did not reduce the risk of serious fall injuries among sedentary older people with functional limitations. These null results were accompanied by suggestive evidence that the physical activity program may reduce the rate of fall related fractures and hospital admissions in men.Trial registration ClinicalsTrials.gov NCT01072500.
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.
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