Recent basic biological research found that obesity accelerates biological aging and increases cardiovascular disease (CVD) risk. However, there is still a lack of real-world population evidence. This study aimed to explore the potential mediation roles of biological age acceleration in the associations between different dimensions of obesity characterization and incident CVD. This international multi-cohort study included participants aged over 45 years with 3 waves longitudinal data from China Health and Retirement Longitudinal Study (CHARLS). China Health and Nutrition Survey (CHNS) was used to develop Klemera-Doubal method-biological age (KDM-BA), and the validation analysis was performed in UK Biobank (UKB) and Hongguang Elderly Health Examination Cohort (HEHEC). Obesity indices including body mass index (BMI), waist circumference (WC), waist height ratio (WtHR), body roundness index (BRI) for body shape; Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP) for visceral fat accumulation; triglyceride-glucose index (TyG) and its derivatives (TyG-BMI, TyG-WC, TyG-WtHR) for metabolic function were used to measure obesity across different dimensions. Biological age acceleration was evaluated by the classic KDM-BA acceleration (KDM-BAacc). Causal mediation analyses assessed the role of biological age acceleration in mediating obesity and incident CVD. In CHARLS, the median follow-up period was 9.00 years, with a baseline age of 58 (52, 65) years. Obesity, KDM-BAacc, and CVD were all significantly associated with each other. For each 1-year increase in KDM-BAacc, the risk of incident stroke, heart disease and CVD increased by 68% (OR 1.68, 95% CI 1.35–2.09), 35% (OR 1.35, 95% CI 1.15–1.59), and 44% (OR 1.44, 95% CI 1.25–1.65), respectively. KDM-BAacc mediated the associations between BMI, WC, WtHR, BRI, CVAI, LAP, TyG-BMI, TyG-WC, TyG-WtHR, with CVD, with the mediation proportions ranging from 10.03 to 25.46%. However, the mediating effect was significant mostly in middle-aged individuals aged 45–65 years. Furthermore, sex differences existed in the mediation mechanisms. Biological age acceleration strongly mediated body shape indices and incident CVD in males, whereas in females, it predominantly mediated visceral fat accumulation and metabolic function dimensions with incident CVD. Similar main results were found in UKB and HEHEC. Biological age acceleration partially mediates the relationship between obesity and incident CVD. This temporal evidence firstly validated the mediation pathway based on international cohorts, emphasizing the importance of addressing biological aging processes in population aged 45–65 years while providing sex-specific obesity intervention strategies to prevent CVD.

Yang X, et al. Diabetes Metab J. 2019 Jan;43:e64. https://doi.org/10.4093/dmj.2019.0081

Background: Choline, an indispensable nutrient, plays a pivotal role in various physiological processes. The available evidence regarding the nexus between dietary choline intake and health outcomes, encompassing cardiovascular disease (CVD), cancer, and all-cause mortality, is limited and inconclusive. This study aimed to comprehensively explore the relationship between dietary choline intake and the aforementioned health outcomes in adults aged > 20 years in the U.S. Methods: This study utilized data from the National Health and Nutrition Examination Survey between 2011 and 2018. Dietary choline intake was evaluated using two 24-h dietary recall interviews. CVD and cancer status were determined through a combination of standardized medical status questionnaires and self-reported physician diagnoses. Mortality data were gathered from publicly available longitudinal Medicare and mortality records. The study utilized survey-weighted logistic and Cox regression analyses to explore the associations between choline consumption and health outcomes. Restricted cubic spline (RCS) analysis was used for dose‒response estimation and for testing for nonlinear associations. Results: In our study of 14,289 participants (mean age 48.08 years, 47.71% male), compared with those in the lowest quintile (Q1), the adjusted odds ratios (ORs) of CVD risk in the fourth (Q4) and fifth (Q5) quintiles of choline intake were 0.70 (95% CI 0.52, 0.95) and 0.65 (95% CI 0.47, 0.90), respectively (p for trend = 0.017). Each 100 mg increase in choline intake was associated with a 9% reduced risk of CVD. RCS analysis revealed a linear correlation between choline intake and CVD risk. Moderate choline intake (Q3) was associated with a reduced risk of mortality, with an HR of 0.75 (95% CI 0.60–0.94) compared with Q1. RCS analysis demonstrated a significant nonlinear association between choline intake and all-cause mortality (P for nonlinearity = 0.025). The overall cancer prevalence association was nonsignificant, except for colon cancer, where each 100 mg increase in choline intake indicated a 23% reduced risk. Conclusion: Elevated choline intake demonstrates an inverse association with CVD and colon cancer, while moderate consumption exhibits a correlated reduction in mortality. Additional comprehensive investigations are warranted to elucidate the broader health implications of choline.

Chaihu-Shugan-San (CHSGS), a noted traditional Chinese medicine formula, has been used as a complementary and alternative therapy for liver fibrosis. However, the antifibrotic mechanisms of CHSGS still remain unclear. Thus, we used network pharmacology approach in combination with single cell and bulk transcriptomics to elucidate the antifibrotic mechanisms of CHSGS. We first screened out 134 bioactive ingredients of CHSGS through the defined criteria. Then, 1150 genes were predicted to be targets for CHSGS, while 625 liver fibrosis-associated genes were identified by single cell transcriptomics analysis. Next, 71 intersecting genes of CHSGS and liver fibrosis were defined as the therapeutic targets in CHSGS against liver fibrosis. Further, 21 core targets and 12 core ingredients of CHSGS against liver fibrosis were also identified. Meanwhile, enrichment analyses of core targets highlighted that the key mechanisms of CHSGS against liver fibrosis include modulation of inflammation responses, inhibition of angiogenesis, and regulation of ECM remodeling, of which the most important mechanism was the regulation of ECM remodeling. The molecular docking simulation validated strong binding affinity between the core targets and core ingredients. Furthermore, 62-gene signature may be used for determining the prognosis in cirrhotic patients based on the results of ssGSEA-Cox analysis. In conclusion, the present study revealed the multiple pharmacological targets and therapeutic mechanisms of CHSGS against liver fibrosis, which may thus serve as an effective antifibrotic therapy. Meanwhile, CHSGS may improve survival of patients with liver cirrhosis by the interaction of 62-gene signature.