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The endocannabinoid system (ECS) participates in regulating whole body energy balance. Overactivation of the ECS has been associated with the negative consequence of obesity and type 2 diabetes. Since activators of the ECS rely on lipid-derived ligands, an investigation was conducted to determine whether dietary PUFA could influence the ECS to affect glucose clearance by measuring metabolites of macronutrient metabolism. C57/blk6 mice were fed a control or DHA-enriched semi-purified diet for a period of 112 d. Plasma, skeletal muscle, and liver were collected after 56 d and 112 d of feeding the diets for metabolomics analysis. Key findings characterized a shift in glucose metabolism and greater catabolism of fatty acids in mice fed the DHA diet. Glucose use and promotion of fatty acids as substrate were found based on levels of metabolic pathway intermediates and altered metabolic changes related to pathway flux with DHA feeding. Greater levels of DHA-derived glycerol lipids were found subsequently leading to the decrease of arachidonate-derived endocannabinoids (eCB). Levels of 1- and 2-arachidonylglcerol eCB in muscle and liver were lower in the DHA diet group compared to controls. These findings demonstrate that DHA feeding in mice alters macronutrient metabolism and may restore ECS tone by lowering arachidonic acid derived eCB.

BACKGROUND: Clinical trials are needed to study topics relevant to older adults with serious illness. Investigators conducting clinical trials with this population are challenged by how to appropriately define, classify, report, and monitor serious and non-serious adverse events (SAEs/AEs), given that some traditionally reported AEs (pressure ulcers, delirium) and SAEs (death, hospitalization) are common in persons with serious illness, and may be consistent with their goals of care. OBJECTIVES: A multi-stakeholder group convened to establish greater clarity on and new approaches to address this critical issue. PARTICIPANTS: Thirty-two study investigators, members of regulatory and sponsor agencies, and patient stakeholders took part. APPROACH: The group met virtually four times and, using a collaborative approach, conducted a survey, select interviews, and reviewed regulatory guidance to collectively define the problem and identify a new approach. RESULTS: SAE/AE challenges fell into two areas: (1) definitions and classifications, including (a) implausible relationships, (b) misalignment with patient-centered care goals, and (c) well-known associations, and (2) reporting and monitoring, including (a) limited guidance, (b) inconsistent standards across regulators, and (c) Data Safety Monitoring Board (DSMB) member knowledge gaps. Problems largely reflected practice norms rather than regulatory requirements that already support context-specific and aggregate reporting. Approaches can be improved by adopting principles that better align strategies for addressing adverse events with the type of intervention being tested, favoring routine and aggregate over expedited reporting, and prioritizing how SAE/AEs relate to patient-centered care goals. Reporting plans and decisions should follow an algorithm underpinned by these principles. CONCLUSIONS: Adoption of the proposed approach-and supporting it with education and better alignment with regulatory guidance and procedures-could improve the quality and efficiency of clinical trials safety involving older adults with serious illness and other vulnerable populations.

People with HIV on combination antiretroviral therapy (ART) have longer life expectancy and are increasingly experiencing age-related comorbidities. Thus, aging with HIV has become a central issue in clinical care and research, which has been particularly challenging with the intersection of the ongoing coronavirus (COVID)-19 pandemic. Since 2009, the International Workshop on HIV and Aging has served as a multidisciplinary platform to share research findings from cross-disciplinary fields along with community advocates to address critical issues in HIV and aging. In this article, we summarize the key oral presentations from the 12th Annual International Workshop on HIV and Aging, held virtually on September 23rd and 24th, 2021. The topics ranged from basic science research on biological mechanisms of aging to quality of life and delivery of care under the COVID-19 pandemic. This workshop enriched our understanding of HIV and aging under the COVID-19 pandemic, identified challenges and opportunities to combat the impact of COVID-19 on HIV communities, and also provided updated research and future directions of the field to move HIV and aging research forward, with the ultimate goal of successful aging for older people with HIV.

This article explores the field of geroscience, which aims to target the biology of aging to prevent or treat age-related diseases. Despite its growing importance, geroscience remains unfamiliar to the general public and many healthcare providers. The article emphasizes the need for collaboration across disciplines and the training of a workforce that can shift from a disease-focused approach to one that targets aging pathways. It also highlights the importance of clear messaging and education to promote geroscience and its potential impact on human health and quality of life. The article discusses the creation of a Geroscience Education and Training Network (GET Network) to address gaps in research education and training. The GET Network aims to revolutionize the training of scientists, educators, and clinicians by providing accessible geroscience education, including shared curricula, a Certificate in Geroscience Research Program, and effective dissemination of educational materials. The network also addresses challenges such as incorporating geroscience into medical student curricula, adapting to the learning styles of millennials, promoting health equity, ensuring the sustainability of educational materials, and combating online antiaging misinformation. Overall, the network seeks to integrate geroscience into medical education and engage students and the public in discussions about geroscience. [Extracted from the article]

The American Geriatrics Society, with support from the National Institute on Aging and other funders, held its eighth Bedside-to-Bench research conference, entitled "Sleep, Circadian Rhythms, and Aging: New Avenues for Improving Brain Health, Physical Health and Functioning," October 4 to 6, 2015, in Bethesda, Maryland. Part of a conference series addressing three common geriatric syndromes-delirium, sleep and circadian rhythm (SCR) disturbance, and voiding dysfunction-the series highlighted relationships and pertinent clinical and pathophysiological commonalities between these three geriatric syndromes. The conference provided a forum for discussing current sleep, circadian rhythm, and aging research; identifying gaps in knowledge; and developing a research agenda to inform future investigative efforts. The conference also promoted networking among developing researchers, leaders in the field of SCR and aging, and National Institutes of Health program personnel.

Background Lower urinary tract syndrome (LUTS) is a group of urinary tract symptoms and signs that can include urinary incontinence. Advancing age is a major risk factor for LUTS; however, the underlying biochemical mechanisms of age-related LUTS remain unknown. Hypoxanthine (HX) is a purine metabolite associated with generation of tissue-damaging reactive oxygen species (ROS). This study tested the hypothesis that exposure of the adult bladder to HX–ROS over time damages key LUT elements, mimicking qualitatively some of the changes observed with aging. Methods Adult 3-month-old female Fischer 344 rats were treated with vehicle or HX (10 mg/kg/day; 3 weeks) administered in drinking water. Targeted purine metabolomics and molecular approaches were used to assess purine metabolites and biomarkers for oxidative stress and cellular damage. Biomechanical approaches assessed LUT structure and measurements of LUT function (using custom-metabolic cages and cystometry) were also employed. Results HX exposure increased biomarkers indicative of oxidative stress, pathophysiological ROS production, and depletion of cellular energy with declines in NAD+ levels. Moreover, HX treatment caused bladder remodeling and decreased the intercontraction interval and leak point pressure (surrogate measure to assess stress urinary incontinence). Conclusions These studies provide evidence that in adult rats chronic exposure to HX causes changes in voiding behavior and in bladder structure resembling alterations observed with aging. These results suggest that increased levels of uro-damaging HX were associated with ROS/oxidative stress-associated cellular damage, which may be central to age-associated development of LUTS, opening up potential opportunities for geroscience-guided interventions. [ABSTRACT FROM AUTHOR]

BackgroundAlthough vitamin D has been mechanistically linked to insulin secretion and sensitivity, it remains unclear whether low 25-hydroxyvitamin D levels confer an increased risk of impaired glucose metabolism. We evaluated the relationship between vitamin D insufficiency (25-hydroxyvitamin D < 20ng/mL) and abnormal hemoglobin A1c (A1c) (≥6.5%) in community-dwelling older persons and examined whether this relationship differed according to race.MethodsParticipants were 2,193 persons of age 70-79 years at Year 1 (52% women; 37% black) in the Health, Aging, and Body Composition study who had clinic visits at Years 2 and 4. Logistic regression analyses, adjusted for potential confounders, were used to evaluate the association between vitamin D insufficiency and abnormal A1c 2 years later. Interaction of race and vitamin D insufficiency was tested.ResultsA total of 665 (30%) and 301 (14%) of the participants had vitamin D insufficiency at Year 2 and abnormal A1c at Year 4, respectively. After controlling for demographics, other potential confounders, and diabetes status at Year 4 (n = 477 diabetics), we found that vitamin D insufficiency was associated with an increased likelihood of having abnormal A1c (odds ratio = 1.56; 95% CI: 1.03-2.37). We also found that this relationship persisted among the 1,765 participants without diabetes in Year 2 (odds ratio = 2.33; 95% CI: 1.00-5.40). Findings did not differ by race.ConclusionsVitamin D insufficiency was associated with abnormal A1c levels among black and white older persons independent of diabetes status. Future studies are needed to establish the temporal relationship between vitamin D and A1c in diverse samples of older persons.