Background The human CISD2 gene is located within a longevity region mapped on chromosome 4q. In mice, Cisd2 levels decrease during natural aging and genetic studies have shown that a high level of Cisd2 prolongs mouse lifespan and healthspan. Here, we evaluate the feasibility of using a Cisd2 activator as an effective way of delaying aging. Methods Hesperetin was identified as a promising Cisd2 activator by herb compound library screening. Hesperetin has no detectable toxicity based on in vitro and in vivo models. Naturally aged mice fed dietary hesperetin were used to investigate the effect of this Cisd2 activator on lifespan prolongation and the amelioration of age-related structural defects and functional decline. Tissue-specific Cisd2 knockout mice were used to study the Cisd2-dependent anti-aging effects of hesperetin. RNA sequencing was used to explore the biological effects of hesperetin on aging. Results Three discoveries are pinpointed. Firstly, hesperetin, a promising Cisd2 activator, when orally administered late in life, enhances Cisd2 expression and prolongs healthspan in old mice. Secondly, hesperetin functions mainly in a Cisd2-dependent manner to ameliorate age-related metabolic decline, body composition changes, glucose dysregulation, and organ senescence. Finally, a youthful transcriptome pattern is regained after hesperetin treatment during old age. Conclusions Our findings indicate that a Cisd2 activator, hesperetin, represents a promising and broadly effective translational approach to slowing down aging and promoting longevity via the activation of Cisd2.
Chronic inflammation, a hallmark of gout, is implicated in the pathogenesis of atherosclerosis. Thus, in theory, gout can be expected to increase the risk of acute myocardial infarction (AMI). Yet, results from several epidemiological studies have been inconclusive. A retrospective cohort study was conducted using the National Health Insurance Research Database of Taiwan dated from 2000 to 2013. The study cohort comprised 3581 patients with gout (the gout cohort) and 14,324 patients without gout (the non-gout cohort). The primary outcome was the incidence of AMI. To estimate the effect of gout on the risk of AMI, the Lunn-McNeil competing risk model was fitted to estimate cause-specific hazard ratios (HRs) and their 95% confidence intervals (CIs). The cumulative incidence of AMI was significantly higher in the gout cohort than in the non-gout cohort, resulting in an adjusted HR of 1.36 (95% CI 1.04 to 2.76). Further, HRs of gout with incident AMI were higher in patients without hypertension, diabetes mellitus, or hyperlipidemia (ranging from 1.63 to 2.09) than in those with each of these comorbidities (ranging from 0.95 to 1.13). The results of this study suggest that patients with gout have an increased risk of AMI. The AMI risk associated with gout was conditional on patients’ cardiovascular risk profile. Future work is needed to confirm these findings.
Homeless individuals have many negative experiences with inequality regarding access to and the use of primary healthcare services, so policies to eliminate the disparities in and barriers to primary care access for these people are needed. The aim of this study was to explore the use and determinants of free hospital outpatient services for homeless people, in order to describe the provision of free healthcare policies for this vulnerable population in Taipei. One cross-sectional survey was conducted to recruit homeless people aged 45 years old and over in Taipei in 2018. A structured questionnaire was used, and face-to-face interviews were conducted by three social workers to collect the data. Finally, 129 participants were recruited in the study. The results show that 81.4% of the homeless people had made free hospital outpatient care visits (mean = 5.9 visits) in the last three months. An unadjusted logistic regression analysis showed that those homeless people who reported having usual healthcare providers, with higher depressive symptom scores, who used medication and had been hospitalized within one year, and had more chronic diseases, were significantly more likely to make free hospital outpatient visits. The adjusted logistic regression model indicates that homeless people with severe depressive symptoms (odds ratio (OR) = 9.32, 95% CI = 1.15–56.07), who had received medication (OR = 3.93; 95% CI = 1.06–14.52), and who had more than five chronic diseases (OR = 1.06, 95% CI = 1.35–13.27), were significantly more likely to make free hospital outpatient visits than their counterparts. The findings highlight that homeless people have higher healthcare requirements than the general population, and the healthcare system should pay more attention to factors associated with higher outpatient service use, such as homelessness, severe depressive symptoms, the receipt of medication and chronic diseases.
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