Lifestyles and their relative contribution to biological aging across multiple organ systems: change analysis from the China Multi-Ethnic Cohort Study

Background Biological aging exhibits heterogeneity across multi organ systems. However, it remains unclear how is lifestyle associated with overall and organ-specific aging and which factors contribute most in Southwest China. Objective To examine the associations of healthy lifestyle with comprehensive and organ-specific biological ages and which factors contribute most. Methods This study involved 8,396 participants who completed two surveys from the China Multi-Ethnic Cohort (CMEC) Study. The healthy lifestyle index (HLI) was developed using five lifestyle factors: smoking, alcohol, diet, exercise, and sleep. The comprehensive and organ-specific biological ages (BAs) were calculated using the Klemera-Doubal method based on longitudinal clinical laboratory measurements, and validation were conducted to select BA reflecting related diseases. Fixed effects model was used to examine associations between HLI or its components and the acceleration of validated BAs. We further evaluated the relative contribution of lifestyle components to comprehension and organ systems BAs using quantile G-computation. Results About two-thirds of participants changed HLI scores between surveys. After validation, three organ-specific BAs (the cardiopulmonary, metabolic, and liver BAs) were identified as reflective of specific diseases and included in further analyses with the comprehensive BA. The health alterations in healthy lifestyle index showed a protective association with the acceleration of all biological ages, with a mean shift of -0.19 (95%CI: -0.34, -0.03) in the comprehensive biological age acceleration. Diet and smoking were the major contributors to overall negative associations of five lifestyle factors with the comprehensive BA and metabolic BA accounting for 24% and 55% respectively. Conclusions Healthy lifestyle changes were inversely related to comprehensive and organ-specific biological aging in Southwest China, with diet and smoking contributing most to comprehensive and metabolic BA separately. Our findings highlight the potential of lifestyle interventions to decelerate aging and identify intervention targets to limit organ-specific aging in less-developed regions. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was primarily supported by the National Natural Science Foundation of China (Grant No. 82273740). The CMEC study was funded by the National Key Research and Development Program of China (Grant No. 2017YFC0907305, 2017YFC0907300). The sponsors had no role in the design, analysis, interpretation, or writing of this article. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Sichuan University Medical Ethical Review Board [ID: K2016038, K2020022]. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data described in the manuscript, code book, and analytic code will be made available by contacting the corresponding author. * ALB : Albumin ALP : Alkaline phosphatase aMED : Alternative Mediterranean diet AST : Aspartate aminotransferase BA : Biological age BMI : Body mass index CVD : Cardiovascular disease CMEC : China Multi-Ethnic Cohort Study CA : Chronological age Cr : Creatinine FEM : Fixed effects model GGT : γ-Glutamyl transpeptidase HBA1C : Glycosylated hemoglobin HLI : Healthy lifestyle index HDL-CH : High-density lipoprotein cholesterol IQR : Interquartile range KDM-BA : Klemera-Doubal method of biological age LDL-CH : Low-density lipoprotein cholesterol MCV : Mean corpuscular volume PEF : Peak expiratory flow PLT : Platelet count QGC : Quantile G-computation SBP : Systolic blood pressure TG : Triglyceride WHR : Waist-to-hip ratio.