Vascular Aging and Atherosclerosis: A Perspective on Aging.

Vascular aging (VA) is recognized as a pivotal factor in the development and progression of atherosclerosis (AS). Although various epidemiological and clinical research has demonstrated an intimate connection between aging and AS, the candidate mechanisms still require thorough examination. This review adopts an aging-centric perspective to deepen the comprehension of the intricate relationship between biological aging, vascular cell senescence, and AS. Various aging-related physiological factors influence the physical system's reactions, including oxygen radicals, inflammation, lipids, angiotensin II, mechanical forces, glucose levels, and insulin resistance. These factors cause endothelial dysfunction, barrier damage, sclerosis, and inflammation for VA and promote AS via distinct or shared pathways. Furthermore, the increase of senescent cells inside the vascular tissues, caused by genetic damage, dysregulation, secretome changes, and epigenetic modifications, might be the primary cause of VA.

Attenuation of allergen-specific immunotherapy for atopic dermatitis by ectopic colonization of Brevundimonas vesicularis in the intestine.

Allergen-specific immunotherapy (AIT) has shown beneficial effects against atopic dermatitis (AD); however, the mechanisms and parameters underlying the efficacy of AIT remain unclear. Here, we report that the community structure and function of the oral and gut microbiota are changed in patients with AD undergoing AIT. Transplantation of fecal microbiota from patients who respond well to AIT improves AD-like dermatitis in mice. The abundance of Brevundimonas vesicularis in the gut of AD patients has been found to be positively correlated with disease severity and is decreased following AIT. Furthermore, we find that B. vesicularis from the oral cavity might ectopically colonize the gut of AD patients. In AD model mice, meanwhile, B. vesicularis promotes the skewing of the Treg/Th17 balance toward Th17 polarization and attenuates the efficacy of ovalbumin-specific immunotherapy. Our findings provide potential strategies for the optimization of AIT for AD via the modulation of the gut microbiota.

Red Yeast Rice Preparations Reduce Mortality, Major Cardiovascular Adverse Events, and Risk Factors for Metabolic Syndrome: A Systematic Review and Meta-analysis.

Background: Metabolic syndrome (MetS) is characterized by the cooccurrence of obesity, insulin resistance, dyslipidaemia, and hypertension. Red yeast rice (RYR) preparations might be beneficial for the prevention and treatment of MetS. Objective: To implement a systematic review and meta-analysis to determine whether RYR preparations improve clinical endpoints and reduce risk factors for MetS. Methods: The PubMed, Cochrane Library, EMBASE, Scopus, China National Knowledge Infrastructure, Chinese VIP Information, and WanFang databases were searched for randomized controlled trials (published up to September 2020), and a meta-analysis was performed using fixed- or random-effects models. The primary outcome measures were mortality and major adverse cardiovascular events (MACEs), and the secondary outcome measures were biochemical parameters of blood glucose, blood lipids, and blood pressure. The registration number is CRD42020209186. Results: A total of 921 articles were identified, of which 30 articles were included in this article. RYR preparations group demonstrated significant improvements in MetS compared with control group. RYR preparations reduced the mortality and MACEs (RR = 0.62, 95% CI [0.49, 0.78]; RR = 0.54, 95% CI [0.43, 0.66]). In terms of blood glucose metabolism, fasting plasma glucose (FPG) (MD = -0.46 mmol/L, 95% CI [-0.71, -0.22]), haemoglobin A1c (HbA1c) (MD = -0.49, 95% CI [-0.71, -0.26]) and the homeostasis model assessment of insulin resistance (HOMA-IR) (MD = -0.93, 95% CI [-1.64, -0.21]) were decreased. Regarding the lipid metabolism, total cholesterol (TC) (MD = -0.74 mmol/L, 95% CI [-1.02, -0.46]), triglycerides (TG) (MD = -0.45 mmol/L, 95% CI [-0.70, -0.21]), and low-density lipoprotein cholesterol (LDL) (MD = -0.42 mmol/L, 95% CI [-0.78, -0.06]) were decreased, while high-density lipoprotein cholesterol (HDL) (MD = 0.14 mmol/L, 95% CI [0.09, 0.20]) was increased. Regarding blood pressure, the mean arterial pressure (MAP) (MD = -3.79 mmHg, 95% CI [-5.01, -2.57]) was decreased. In addition, RYR preparations did not increase the incidence of adverse reactions (RR = 1.00, 95% CI [0.69, 1.43]). Conclusion: RYR preparations reduce mortality, MACEs, and multiple risk factors for MetS without compromising safety, which supports its application for the prevention and treatment of MetS. However, additional high-quality studies are needed to provide more evidence for the effect of RYR on MetS due to the heterogeneity in this study. Systematic Review Registration: www.crd.york.ac.uk/PROSPERO, identifier CRD42020209186.

Multidimensional single-cell analysis of human peripheral blood reveals characteristic features of the immune system landscape in aging and frailty.

Frailty is an intermediate status of the human aging process, associated with decompensated homeostasis and death. The immune phenotype of frailty and its underlying cellular and molecular processes remain poorly understood. We profiled 114,467 immune cells from cord blood, young adults and healthy and frail old adults using single-cell RNA and TCR sequencing. Here we show an age-dependent accumulation of transcriptome heterogeneity and variability in immune cells. Characteristic transcription factors were identified in given cell types of specific age groups. Trajectory analysis revealed cells from non-frail and frail old adults often fall into distinct paths. Numerous TCR clonotypes were shared among T-cell subtypes in old adults, indicating differential pluripotency and resilience capabilities of aged T cells. A frailty-specific monocyte subset was identified with exclusively high expression of long noncoding RNAs NEAT1 and MALAT1. Our study discovers human frailty-specific immune cell characteristics based on the comprehensive dimensions in the immune landscape of aging and frailty.

A research agenda for ageing in China in the 21st century (2nd edition): Focusing on basic and translational research, long-term care, policy and social networks.

One of the key issues facing public healthcare is the global trend of an increasingly ageing society which continues to present policy makers and caregivers with formidable healthcare and socio-economic challenges. Ageing is the primary contributor to a broad spectrum of chronic disorders all associated with a lower quality of life in the elderly. In 2019, the Chinese population constituted 18 % of the world population, with 164.5 million Chinese citizens aged 65 and above (65+), and 26 million aged 80 or above (80+). China has become an ageing society, and as it continues to age it will continue to exacerbate the burden borne by current family and public healthcare systems. Major healthcare challenges involved with caring for the elderly in China include the management of chronic non-communicable diseases (CNCDs), physical frailty, neurodegenerative diseases, cardiovascular diseases, with emerging challenges such as providing sufficient dental care, combating the rising prevalence of sexually transmitted diseases among nursing home communities, providing support for increased incidences of immune diseases, and the growing necessity to provide palliative care for the elderly. At the governmental level, it is necessary to make long-term strategic plans to respond to the pressures of an ageing society, especially to establish a nationwide, affordable, annual health check system to facilitate early diagnosis and provide access to affordable treatments. China has begun work on several activities to address these issues including the recent completion of the of the Ten-year Health-Care Reform project, the implementation of the Healthy China 2030 Action Plan, and the opening of the National Clinical Research Center for Geriatric Disorders. There are also societal challenges, namely the shift from an extended family system in which the younger provide home care for their elderly family members, to the current trend in which young people are increasingly migrating towards major cities for work, increasing reliance on nursing homes to compensate, especially following the outcomes of the 'one child policy' and the 'empty-nest elderly' phenomenon. At the individual level, it is important to provide avenues for people to seek and improve their own knowledge of health and disease, to encourage them to seek medical check-ups to prevent/manage illness, and to find ways to promote modifiable health-related behaviors (social activity, exercise, healthy diets, reasonable diet supplements) to enable healthier, happier, longer, and more productive lives in the elderly. Finally, at the technological or treatment level, there is a focus on modern technologies to counteract the negative effects of ageing. Researchers are striving to produce drugs that can mimic the effects of 'exercising more, eating less', while other anti-ageing molecules from molecular gerontologists could help to improve 'healthspan' in the elderly. Machine learning, 'Big Data', and other novel technologies can also be used to monitor disease patterns at the population level and may be used to inform policy design in the future. Collectively, synergies across disciplines on policies, geriatric care, drug development, personal awareness, the use of big data, machine learning and personalized medicine will transform China into a country that enables the most for its elderly, maximizing and celebrating their longevity in the coming decades. This is the 2nd edition of the review paper (Fang EF et al., Ageing Re. Rev. 2015).

Impaired glucose tolerance predicts all-cause mortality among older men at high risk for cardiovascular disease in China.

AIMS: To investigate the potential association between impaired glucose tolerance (IGT) and all-cause mortality among older men at high risk for cardiovascular disease (CVD) in China. METHODS: In this prospective observational study, 460 older men aged ≥60 years were determined to have either IGT or normal glucose tolerance (NGT) based on an oral glucose tolerance test conducted between May 2005 and May 2007. IGT and NGT were diagnosed according to the 1999 WHO diagnostic criteria. All subjects were followed until March 2017. The primary outcome studied was all-cause mortality. Multivariate Cox models were used to estimate relative risk for all-cause mortality. RESULTS: During a mean follow-up of 11.2 years, forty-three (21.4%) subjects in the IGT group and twenty-nine (11.2%) subjects in the NGT group died (HR 2.05, 95% CI 1.28-3.28, P=0.003). Multivariate Cox proportional-hazards analysis demonstated that IGT was significantly associated with increased risk for all-cause mortality, composite cardiovascular outcome, nonfatal stroke and heart failure after adjusting for potential confounding factors. Logistic regression analysis showed that IGT at baseline (P<0.05) rather than incident type 2 diabetes was a risk factor of all-cause mortality. CONCLUSIONS: IGT was significantly associated with all-cause mortality in older Chinese men at high risk for CVD.