Modulators of platelet function in aging

Abstract

Platelets are small, anucleated effector cells that play an important role in linking the hemostatic and inflammatory processes in the body. Platelet function is known to be altered under various inflammatory conditions including aging. A gain in platelet function during aging can increase the risk of thrombotic events, such as stroke and acute myocardial infarction. Anti-platelet therapy is designed to reduce risk of serious cerebrovascular and cardiovascular events, but the adverse consequences of therapy, such as risk for bleeding increases with aging as well. Age-associated comorbidities such as obesity, diabetes, and hyperlipidemia also contribute to increased platelet activity and thus can enhance the risk of thrombosis. Therefore, identification of unique mechanisms of platelet dysfunction in aging and in age-associated comorbidities is warranted to design novel antiplatelet drugs. This review outlines some of the current areas of research on aging-related mechanisms of platelet hyperactivity and addresses the clinical urgency for designing anti-platelet therapies toward novel molecular targets in the aging population.     

滋阴药延缓衰老机制的研究进展＊

当代社会，老年人口比例呈现不断上升的趋势，老龄化问题日益严峻。因此，如何有效地延缓衰老不仅成为了世界医学研究的热点，也成为了全球亟待解决的问题。中医药在延缓衰老方面经验丰富，而滋阴药在此类研究中效果显著。本文通过整理滋阴药抗衰老作用机制的若干文献，对滋阴复方六味地黄丸、二至丸、左归丸及其他滋阴中药延缓衰老的机制研究进展进行综述。     

Intravesical Bacillus Calmette-Guérin Treatment Is Inversely Associated With the Risk of Developing Alzheimer Disease or Other Dementia Among Patients With Non–muscle-invasive Bladder Cancer

BackgroundThe immune system plays an important role in the pathogenesis of Alzheimer disease (AD), but it remains unclear whether bacillus Calmette-Guérin (BCG) may affect the risk of AD or not.MethodsUsing retrospective chart review, we collected data regarding demographics, comorbidities, cancer diagnosis, BCG treatment, and subsequent diagnosis of AD or other dementia in a racially/ethnically diverse cohort of patients with non–muscle-invasive bladder cancer (NIMBC) receiving treatment between 1984 and 2020 in the Bronx, New York. We used Cox proportional hazard models to examine association between BCG treatment and risk of incident AD or other dementia, adjusting for age, gender, race/ethnicity, and major comorbidities.ResultsIn our cohort of 1290 patients with NMIBC, a total of 99 (7.7%) patients developed AD or other dementia during follow-up. Patients who received BCG treatment (25%) had a 60% lowered incidence of AD or other dementia (adjusted hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.21-0.80) in comparison to those who did not receive BCG. There was also suggestive evidence that the reduction in risk of AD or other dementia associated with BCG treatment was stronger in men (adjusted HR, 0.34; 95% CI, 0.15-0.81) but not in women (adjusted HR, 0.75; 95% CI 0.25-2.24). When we stratified the patients who received BCG by type of treatments, patients who received both induction and maintenance rounds of BCG had a further lowered incidence of AD or other dementia (HR, 0.23; 95% CI, 0.06-0.96) than patients who did not receive BCG.ConclusionsTo our knowledge, our study is one of the first to suggest that BCG treatment is associated with a reduced risk of developing AD or other dementia in a multiethnic population, independent of significant comorbidities. Larger cohort studies are needed to corroborate our findings.     

Aging changes agonist induced contractile responses in permeabilized rat bladder

Aging alters bladder functions where a decrease in filling, storage and emptying is observed. These changes cause urinary incontinence, especially in women. The aim of this study is to examine how aging affects the intracellular calcium movements due to agonist-induced contractions in permeabilized female rat bladder. Urinary bladder isolated from young and old female Sprague-Dawley rats were used. Small detrusor strips were permeabilized with β-escin. The contractile responses induced with agonists were compared between young and old groups. Carbachol-induced contractions were decreased in permeabilized detrusor from old rats compared to young group. Heparin and ryanodine decreased carbachol-induced contractions in young rats where only heparin inhibited these contractions in olds. Caffeine-induced contractions but not inositol triphosphate (IP₃)-induced contractions were decreased in old group compared to youngs. The cumulative calcium response curves (pCa 8–4) were also decreased in old rats. Carbachol-induced calcium sensitization responses did not alter by age where GTP-β-S and GF-109203X but not Y-27632 inhibited these responses. Carbachol-induced contractions decrease with aging in rat bladder detrusor. It can be postulated as IP₃-induced calcium release (IICR) is primarily responsible for the contractions in older rats where the decrease in carbachol contractions in aging may be as a result of a decrease in calcium-induced calcium release (CICR), rather than carbachol-induced calcium sensitization.     

Putting age-related task activation into large-scale brain networks: A meta-analysis of 114 fMRI studies on healthy aging

Normal aging is associated with cognitive decline and underlying brain dysfunction. Previous studies concentrated less on brain network changes at a systems level. Our goal was to examine these age-related changes of fMRI-derived activation with a common network parcellation of the human brain function, offering a systems-neuroscience perspective of healthy aging. We conducted a series of meta-analyses on a total of 114 studies that included 2035 older adults and 1845 young adults. Voxels showing significant age-related changes in activation were then overlaid onto seven commonly referenced neuronal networks. Older adults present moderate cognitive decline in behavioral performance during fMRI scanning, and hypo-activate the visual network and hyper-activate both the frontoparietal control and default mode networks. The degree of increased activation in frontoparietal network was associated with behavioral performance in older adults. Age-related changes in activation present different network patterns across cognitive domains. The systems neuroscience approach used here may be useful for elucidating the underlying network mechanisms of various brain plasticity processes during healthy aging.     

Association between sarcopenia and diabetes in community dwelling elderly in the Amazon region – Viver Mais Project

BackgroundStudies indicate the intrinsic relationship between sarcopenia and diabetes mellitus (DM) pathophysiological mechanisms. Changes in insulin and muscular metabolism are features of diabetic patients and can interact as sarcopenic accelerators. Conversely, sarcopenic patients feature lower glucose tolerance and higher serum insulin levels, predisposing them to DM.ObjectiveTo study the association between sarcopenia and DM in a community-dwelling elderly population of the Amazon region.MethodsCross-sectional study, performed in Belém, Brazil, with 1078 patients aged above 60 years old from the Viver Mais Project (VMP). The definition of sarcopenia was based in the European Working Group on Sarcopenia in Older People (EWGSOP). Calf circumference >31 cm was considered normal, muscle strength was discriminated by BMI and measured with the hand grip test, and gait speed <0.8 m/s configured low performance. DM was diagnosed when reported by the patient or medical form, use of hypoglycemic medications/insulin and in the presence of fasting glucose >126 mg/dl or glycated hemoglobin (HbA1c) >6.5% on two occasions. Other medical and socio-demographic data were extracted from medical forms.ResultsThe frequency of sarcopenia was 9.4%, while DM was present in 36.87% of the patients, and had an increased occurrence in the sarcopenic group. Female sex, advanced age, DM, coronary insufficiency, osteoporosis, body mass index, waist circumference, triglycerides and functionality were associated with sarcopenia. In multivariate analysis, sarcopenia remained strongly associated with DM (OR: 3.208, 95%CI: 1.784–5.769).ConclusionThis study describes strong and independent association between sarcopenia and DM. To further clarify these findings, broader prospective cohorts are necessary.     

Age-related variations in gene expression patterns of renal cell carcinoma

Background

Clear cell renal cell carcinoma (ccRCC) is known to occur across the adult lifetime traversing the spectrum of age-related organismal changes. Little is known as to how the aging process may affect the course of renal cell carcinoma (RCC) and the repertoire of genes involved.