Translational research : the journal of laboratory and clinical medicine
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The age-associated decline in muscle mass has become synonymous with physical frailty among the elderly due to its major contribution in reduced muscle function. Alterations in protein and redox homeostasis along with chronic inflammation, denervation, and hormonal dysregulation are all hallmarks of muscle wasting and lead to clinical sarcopenia in older adults. Reduction in skeletal muscle mass has been observed and reported in the scientific literature for nearly 2 centuries; however, identification and careful examination of molecular mediators of age-related muscle atrophy have only been possible for roughly 3 decades. Here we review molecular targets of recent interest in age-related muscle atrophy and briefly discuss emerging small molecule therapeutic treatments for muscle wasting in sarcopenic susceptible populations.
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Frailty and cognitive impairment are among the 2 most common geriatric syndromes. Their presence poses major risks to the elderly including greater disability, reduced quality of life, and higher morbi-mortality. Recent evidence suggest that frailty can be a risk factor for incident dementia. ⋯ Here, we will review the current evidence of the association between frailty and cognitive impairment. We will also review the possible biological mechanistic links between the 2 conditions. Finally, we will address potential therapeutic targets and interventions that can mitigate both conditions.
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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.