Dynamics of serum testosterone and biological aging in men: insights from Chinese, American, and British populations

Background: Biological age (BA) is considered a better predictor of aging than chronological age (CA). BA acceleration was defined as the disparity between BA and CA. However, there has been inconclusive evidence on whether BA acceleration might be reversed by increased total testosterone (TT). The goal of this cross-sectional study was to investigate the relationship between TT and BA acceleration. Methods: Klemera and Doubal method biological age (KDM-BA) was employed as an indicator of BA in this study. This study involved participants of three ancestries from five cohorts, including the National Health and Nutrition Examination Survey (NHANES, recruited between 1 January 2011 and 31 December 2016), West China Health and Aging Trend (WCHAT, recruited between 1 January 2018 and 31 December 2018), West China Natural Population Cohort Study (WCNPCS, recruited between 1 January 2019 and 31 December 2020), UK Biobank (UKB, recruited between 3 March 2016 and 1 October 2020), and the West China Hospital robot-assisted radical prostatectomy (RARP) cohort (recruited between 1 January 2017 and 31 December 2023). Association between serum TT and BA acceleration were assessed by multivariable linear regression in NHANES, WCHAT, and WCNPCS. Change-to-change analysis was performed to evaluate the association between the dynamic of serum TT and BA acceleration in the UKB. 38 prostate cancer patients underwent adjuvant androgen deprivation therapy (ADT) were included to exploring whether ADT deteriorates BA acceleration. Findings: A total of 6976, 2080, 2133, and 6058 participants from NHANES, WCHAT, WCNPCS, and UKB, respectively, were included in the study. Higher serum TT was consistently associated with attenuated BA acceleration across NHANES, WCHAT, and WCNPCS. In UKB, Box-Cox with negatives allowed (BCN)-transformed relative TT change was significantly associated with decreased BCN-transformed BA acceleration change (β: -0.047, 95% CI: -0.057 to -0.038). The results were remained robust in the stratification analysis, restricted cubic spline regression (RCS), and sensitivity analysis. The pre-and-post ADT paired test further indicated the deprivation of TT accelerated biological aging of prostate cancer patients. Interpretation: This study reveals that higher serum TT was associated with reduced biological aging. Men with increased serum TT on repeat testing demonstrated reduced BA acceleration. Comparison of men with prostate cancer revealed advanced BA acceleration after receiving ADT. This study suggests TT may be a reasonable indicator for biological aging. Funding: National key research and development program of China, Programs from Science and Technology Department of Sichuan Province, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University.