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Background: Mild-to-moderate chronic kidney disease (CKD G3a) is prevalent in older adults. Substantial evidence suggests that individuals with advanced CKD face a high risk for common geriatric conditions, like functional impairment and cognitive decline, whereas the relationships between mild-to-moderate CKD and functional impairment and cognitive decline, but also poor nutritional status and mood disorders, are still unclear. Objective: The aim of this study was to explore associations between mild-to-moderate CKD and impairments in the core domains of geriatric assessment (GA) in a large cohort of community-dwelling older adults. Methods: This was a cross-sectional analysis of 1,476 participants of the Berlin Aging Study II. Study participants were stratified as to presence or absence of CKD G3a (estimated glomerular filtration rate [eGFR] 45-59 mL/min/1.73 m<sup>2</sup> vs. eGFR ≥60 mL/min/1.73 m<sup>2</sup>). GA comprised the following instruments: the Activities of Daily Living Scale (ADL), the Timed up and Go (TUG), the Tinetti test (Tinetti), the Mini-Mental-State Examination (MMSE), the Geriatric Depression Scale (GDS), and the Mini Nutritional Assessment (MNA). We used logistic regression models to estimate multivariable-adjusted associations between CKD G3a and impairments in the respective domains. Results: A total of 282 subjects with mild-to-moderate CKD (CKD G3a) were identified (19.1%). Overall, the prevalence of impairments identified was higher among subjects with compared to without CKD G3a (21 vs. 15.9%, p = 0.043). In multivariable-adjusted models, CKD G3a was consistently associated with increased odds of an impaired gait performance as to the TUG (adjusted odds ratio 2.06, 95% CI 1.04-4.09). In contrast, on average, individuals with and without CKD G3a did not differ as to their results in the MMSE, the ADL, the MNA, and the GDS. Conclusion: GA identified impairments in 21 versus 15.9% of older adults with and without mild-to-moderate CKD, respectively. However, except for an increased likelihood of impaired gait performance (TUG) with mild-to-moderate CKD, we did not find independent associations between mild-to-moderate CKD and geriatric conditions.
Abstract
Caveolae position CaV3.2 (T‐type Ca2+ channel encoded by the α‐3.2 subunit) sufficiently close to RyR (ryanodine receptors) for extracellular Ca2+ influx to trigger Ca2+ sparks and large‐conductance Ca2+‐activated K+ channel feedback in vascular smooth muscle. We hypothesize that this mechanism of Ca2+ spark generation is affected by age. Using smooth muscle cells (VSMCs) from mouse mesenteric arteries, we found that both Cav3.2 channel inhibition by Ni2+ (50 µM) and caveolae disruption by methyl‐ß‐cyclodextrin or genetic abolition of Eps15 homology domain‐containing protein (EHD2) inhibited Ca2+ sparks in cells from young (4 months) but not old (12 months) mice. In accordance, expression of Cav3.2 channel was higher in mesenteric arteries from young than old mice. Similar effects were observed for caveolae density. Using SMAKO Cav1.2−/− mice, caffeine (RyR activator) and thapsigargin (Ca2+ transport ATPase inhibitor), we found that sufficient SR Ca2+ load is a prerequisite for the CaV3.2‐RyR axis to generate Ca2+ sparks. We identified a fraction of Ca2+ sparks in aged VSMCs, which is sensitive to the TRP channel blocker Gd3+ (100 µM), but insensitive to CaV1.2 and CaV3.2 channel blockade. Our data demonstrate that the VSMC CaV3.2‐RyR axis is down‐regulated by aging. This defective CaV3.2‐RyR coupling is counterbalanced by a Gd3+ sensitive Ca2+ pathway providing compensatory Ca2+ influx for triggering Ca2+ sparks in aged VSMCs.
Over the past decades, the human life span has dramatically increased, and therefore, a steady increase in diseases associated with age (such as Alzheimer’s disease and Parkinson’s disease) is expected. In these neurodegenerative diseases, there is a cognitive decline and memory loss, which accompany increased systemic inflammation, the inflamm-aging, and the insulin resistance. Despite numerous studies of age-related pathologies, data on the contribution of brain insulin resistance and innate immunity components to aging are insufficient. Recently, much research has been focused on the consequences of nutrients and adiposity- and nutrient-related signals in brain aging and cognitive decline. Moreover, given the role of metainflammation in neurodegeneration, lifestyle interventions such as calorie restriction may be an effective way to break the vicious cycle of metainflammation and have a role in social behavior. The various effects of calorie restriction on metainflammation, insulin resistance, and neurodegeneration have been described. Less attention has been paid to the social determinants of aging and the possible mechanism by which calorie restriction might influence social behavior. The purpose of this review is to discuss current knowledge in the interdisciplinary field of geroscience—immunosenescence, inflamm-aging, and metainflammation—which makes a significant contribution to aging. A substantial part of the review is devoted to frontiers in the brain insulin resistance in relation to neuroinflammation. In addition, we summarize new data on potential mechanisms of calorie restriction that influence as a lifestyle intervention on the social brain. This knowledge can be used to initiate successful aging and slow the onset of neurodegenerative diseases.