Translational research : the journal of laboratory and clinical medicine
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Microbiota derived short chain fatty acids (SCFAs) are produced by fermentation of nondigestible fiber, and are a key component in intestinal barrier homeostasis. Since the microbiome has diurnal fluctuations, we hypothesized that SCFAs in humans have a diurnal rhythm and their rhythmicity would be impacted by the host central circadian misalignment (night shift work) which would make intestinal barrier more susceptible to disruption by alcohol. To test this hypothesis, we studied 3 groups of subjects: patients with alcohol use disorder, but no liver disease (AD), healthy day workers (DW), and night workers (NW). ⋯ Both chronic and moderate alcohol consumption for 1 week caused circadian disruption based on wrist actigraphy and urinary melatonin. Our study shows that (1) gut-derived plasma SCFAs have a diurnal rhythm in humans that is impacted by the central clock of the host; (2) moderate alcohol suppresses SCFAs which was associated with increased colonic permeability; and (3) less invasive urinary 6-SM correlated and rest-activity actigraphy correlated with plasma melatonin. Future studies are needed to examine the role circadian misalignment on gut derived SCFAs as possible mechanism for loss of intestinal barrier resiliency to injurious agents like alcohol.
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Frailty is a clinical state of vulnerability to stressors resulting from cumulative alterations in multiple physiological and molecular systems. Frailty assessment in patients with chronic disease is useful for identifying those who are at increased risk for poor clinical and patient reported outcomes. ⋯ Herein, we review the literature and potential pathobiological mechanisms underpinning associations between frailty in lung disease and age, sex, comorbidity and symptom burden, severity of lung disease, inflammatory biomarkers, various clinical parameters, body composition measures, and physical activity levels. We also propose a multipronged program of future research focused on improving the accuracy and precision of frailty measurement in lung disease, identifying blood-based biomarkers and measures of body composition for frailty, determining whether subphenotypes of frailty with distinct pathobiology exist, and developing personalized interventions that target the specific underlying mechanisms causing frailty.
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The human microbiome is constituted by an extensive network of organisms that lie at the host/environment interface and transduce signals that play vital roles in human health and disease across the lifespan. Frailty is a critical aging-related syndrome marked by diminished physiological reserve and heightened vulnerability to stress, predictive of major adverse clinical outcomes including death. ⋯ We discuss HIV infection as a key prototype for elucidating the complex pathways via which the microbiome may precipitate frailty. Finally, we review considerations for future research efforts.
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Frailty is a complex late life phenotype characterized by cumulative declines in multiple physiological systems that increases the risk for disability and mortality. The biological changes associated with aging are risk factors for frailty as well as for complex diseases; whereas longevity is assumed to be an outcome of protective biological mechanisms. ⋯ The complexity of these phenotypes and relatively low heritability in studies are the main roadblocks in deciphering genetic mechanisms of these age associated conditions. We review genetic research related to frailty, and discuss the possible intertwined biology of frailty and longevity.
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There are over 15 million survivors of cancer in the United States whose rates of frailty, an aging phenotype, range from just under 10% to over 80%. Frailty impacts not only disease survival but also long-term function and quality of life in children, adolescents, and in all adults diagnosed and/or treated for cancer. ⋯ Biological mechanisms responsible for aging and potentially for frailty among individuals with or who have been treated for cancer are discussed. Finally, promising pharmaceutical and lifestyle interventions designed to impact aging rather than a specific disease, tested in other populations, but likely applicable in cancer patients and survivors, are discussed.