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There is growing interest in understanding how ethanol use interacts with advancing age to influence the brain and cognition. Animal models are employed to investigate the cellular and molecular mechanisms of brain aging and age-related neurodegenerative diseases that underlie cognitive decline. However, all too often research on problems and diseases of the elderly are conducted in healthy young animals, providing little clinical relevance. The validity of animal models is discussed, and confounds due to age-related differences in anxiety, sensory-motor function, and procedural learning are highlighted in order to enhance the successful translation of preclinical results into clinical settings. The mechanism of action of ethanol on brain aging will depend on the dose, acute or chronic treatment, or withdrawal from treatment and the age examined. Due to the fact that humans experience alcohol use throughout life, important questions concern the effects of the dose and duration of ethanol treatment on the trajectory of cognitive function. Central to this research will be questions of the specificity of alcohol effects on cognitive functions and related brain regions that decline with age, as well as the interaction of alcohol with mechanisms or biomarkers of brain aging. Alternatively, moderate alcohol use may provide a source of reserve and resilience against brain aging. Longitudinal studies have the advantage of being sensitive to detecting the effects of treatment on the emergence of cognitive impairment in middle age and can minimize effects of stress/anxiety associated with the novelty of alcohol exposure and behavioral testing, which disproportionately influence aged animals. Finally, the effect of alcohol on senescent neurophysiology and biomarkers of brain aging are discussed. In particular, the interaction of age and effects of alcohol on inflammation, oxidative stress, N-methyl- d -aspartate receptor function, and the balance of excitatory and inhibitory synaptic transmission are highlighted. • An overview of validity of animal models for examining alcohol effects on brain aging is provided. • Advantages of longitudinal studies for minimizing confounds are discussed. • Specificity of effects on cognitive function and related brain regions are discussed. • Alcohol effects on senescent neurophysiology and biomarkers of brain aging are discussed. • Alcohol may affect susceptibility to brain aging or reserve and resilience. [ABSTRACT FROM AUTHOR]

• Cognitive reserve represents plastic properties to maintain cognition in the face of brain aging. • Statistical filtering across age identified brain aging genes. • Cognitive reserve genes predicted better-than-expected cognition for a given level of brainaging. Variability in cognitive decline is related to the environment, lifestyle factors, and individual differences in biological aging, including cognitive reserve, plastic properties of the brain, which account for better-than-expected cognition for a given level of brain aging or pathology. Cognitive reserve has not been thoroughly investigated in aged rodents. To address this gap, cognitive reserve was examined using Gene Expression Omnibus data for the CA1 region of the hippocampus of young and aged behaviorally characterized male rats. Statistical filtering identified brain aging and potential cognitive reserve genes, and multiple regression was employed to confirm cognitive reserve genes as genes that predicted better-than-expected cognition for a given level of brain aging. In general, cognitive reserve genes, in which increased expression was associated with better cognition, were not different with age or directly correlated with measures of cognition and appear to act as negative regulators of aging processes, including neuroinflammation and oxidative stress. The results suggest that, for some animals, resilience mechanisms are activated to counteract aging stressors that impair cognition. In contrast, cognitive reserve genes, in which decreased expression was associated with better cognition, were linked to nervous system development and cation transport, suggesting adaptive changes in the circuit to preserve cognition. [ABSTRACT FROM AUTHOR]

Deep tissue abscesses represent a significant source of morbidity and hospital stay, with standard of care drainage failing in many cases. We investigated photodynamic therapy (PDT) as an adjunct to standard of care, to reduce or eliminate bacterial burden. A Phase 1 clinical trial was performed to evaluate safety and feasibility of methylene blue (MB) PDT at the time of abscess drainage. Immediately following drainage, MB-PDT was performed. Diffuse reflectance spectroscopy was performed to evaluate abscess wall optical properties. No study-related adverse events were noted, and no side effects were observed. PDT was well tolerated by all subjects, and infused MB was recovered in all cases. Optical property measurements showed variability in hemoglobin concentration and oxygenation, as well as MB uptake, between subjects. MB-PDT at the time of percutaneous abscess drainage was safe and feasible, and optical property measurements showed wide variance between subjects. [ABSTRACT FROM AUTHOR]

An estimated 250 million people worldwide suffer from knee osteoarthritis (KOA), with older adults having greater risk. Like other age-related diseases, residents of high-deprivation neighborhoods experience worse KOA pain outcomes compared to their more affluent neighbors. The purpose of this study was to examine the relationship between neighborhood deprivation and pain severity in KOA and the influence of epigenetic age acceleration (EpAA) on that relationship. The sample of 128 participants was mostly female (60.9%), approximately half non-Hispanic Black (49.2%), and had a mean age of 58 years. Spearman bivariate correlations revealed that pain severity positively correlated with EpAA (ρ = 0.47, p ≤ 0.001) and neighborhood deprivation (ρ = 0.25, p = 0.004). We found a positive significant relationship between neighborhood deprivation and EpAA (ρ = 0.47, p ≤ 0.001). Results indicate a mediating relationship between neighborhood deprivation (predictor), EpAA (mediator), and pain severity (outcome variable). There was a significant indirect effect of neighborhood deprivation on pain severity through EpAA, as the mediator accounted for a moderate portion of the total effect, PM = 0.44. Epigenetic age acceleration may act as a mechanism through which neighborhood deprivation leads to worse KOA pain outcomes and may play a role in the well-documented relationship between the neighborhood of residence and age-related diseases. • Neighborhood deprivation is associated with worse knee osteoarthritis pain severity. • Epigenetic age acceleration shows a mediating relationship in this phenomenon. • Epigenetic aging may act as mechanism for socioeconomic - health outcomes link. [ABSTRACT FROM AUTHOR]

Knee pain is a leading cause of disability in the aging population and may indirectly accelerate biological aging processes. Chronological aging increases the risk of developing of knee pain and knee pain reduces physical function; however, limited data exist on how epigenetic aging, a known hallmark of biological aging shown to predict health span and mortality, may influence this relationship. The purpose of this study was to examine whether decreased physical performance associated with knee pain is mediated by markers of epigenetic aging. Participants (57.91 ± 8.04 years) with low impact knee pain (n = 95), high impact knee pain (n = 53) and pain-free controls (n = 26) completed self-reported pain, a blood draw and a short physical performance battery (SPPB) that included balance, walking, and sit to stand tasks. We employed an epigenetic clock previously associated with knee pain and shown to predict overall mortality risk (DNAmGrimAge). Bootstrapped-mediation analyses were used to determine associations of DNAmGrimAge and SPPB between pain groups. Those with high impact and low impact pain had a biologically older epigenetic age (5.14y ± 5.66 and 1.32y ± 5.41, respectively). However, while there were direct effects of pain on overall physical performance, these were not explained by epigenetic aging. Epigenetic aging only mediated the effect of pain on balance performance. Future work is needed to examine pain's impact on biological aging processes including epigenetic aging and its ultimate effect on physical function measures known to predict health span and mortality. • DNAmGrimAge is an epigenetic clock associated with pain and physical function. • An older epigenome is related to worse physical function, particularly balance. • Epigenetic aging mediated the effect of pain on balance performance. • Future work should examine pain's impact on biological aging and physical function. [ABSTRACT FROM AUTHOR]

The role of endogenous bile acids as lipid stabilizers aiding uptake of lipophilic nutrients via micelle formation and saponification effects is well documented and precedes their growing applications in pharmaceutical sciences. Their utility stems from their unique physico-chemical profile and ability to modulate immune cell signalling pathways. It has been shown that bile acids alter specific receptor-mediated pathways of cellular respiration and metabolism, providing potential clinical therapies for cardio-metabolic disorders such as diabetes mellitus, hypercholesterolemia, and heart disease. Additionally, some bile acids exert profound anti-oxidant, anti-inflammatory and immunosuppressant properties, and are effective at reducing blood pressure and alleviating hypertension. Their unique amphoteric properties and proven ability as permeability enhancers make them a desirable pharmaceutical excipient. When incorporated with various carbohydrates, polymers, hydrogels and/or polyelectrolytes to form micro- or nano-capsules, they provide enhanced thermodynamic, osmotic and structural stability, and cater for controlled delivery via specific tissue targeting, pH dependant release and temperature guided sol-gel complexation. Additionally, due to their immunosuppressant properties, they enhance the immunogenicity of encapsulated cells, increasing the feasibility of bioartificial organs as transplantable therapeutics. This review explores existing and future applications of bile acids and provides a synopsis of their role in advanced, novel therapeutic delivery systems. [ABSTRACT FROM AUTHOR]