Huang Weichao, Deng Linghui, Wen Qiaorui, Zhang Zilong, Yue Jirong, Zhang Chichen, Zhou Xianghong, Jin Yuming, Hu Dan, Jiang Zhongyuan, Manuel Colucci, Daniele Robesti, Aurora Valdata, Zou Xiaoli, Zhan Yu, Chen Lei, Luo Shaoheng, Sophia Zuoqiu, Wei Qiang, Yang Lu, Dong Birong, Wang Shengfeng, Qiu Shi
Department of Urology, Institute of Urology and National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.
National Clinical Research Center of Geriatrics, The Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
EClinicalMedicine. 2025 Apr 1;82:103178. doi: 10.1016/j.eclinm.2025.103178. eCollection 2025 Apr.
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.
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.
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.
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.
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.
生物学年龄（BA）被认为是比实际年龄（CA）更好的衰老预测指标。BA加速被定义为BA与CA之间的差异。然而，关于增加总睾酮（TT）是否可能逆转BA加速，目前证据尚无定论。这项横断面研究的目的是调查TT与BA加速之间的关系。
本研究采用克莱梅拉和杜巴尔方法生物学年龄（KDM-BA）作为BA的指标。本研究纳入了来自五个队列的三个血统的参与者，包括国家健康和营养检查调查（NHANES，2011年1月1日至2016年12月31日招募）、华西健康与衰老趋势研究（WCHAT，2018年1月1日至2018年12月31日招募）、华西自然人群队列研究（WCNPCS，2019年1月1日至2020年12月31日招募）、英国生物银行（UKB，2016年3月3日至2020年10月1日招募）以及华西医院机器人辅助根治性前列腺切除术（RARP）队列（2017年1月1日至2023年12月31日招募）。在NHANES、WCHAT和WCNPCS中，通过多变量线性回归评估血清TT与BA加速之间的关联。在UKB中进行变化对变化分析，以评估血清TT动态与BA加速之间的关联。纳入38例接受辅助雄激素剥夺治疗（ADT）的前列腺癌患者，以探讨ADT是否会加剧BA加速。
本研究分别纳入了来自NHANES、WCHAT、WCNPCS和UKB的6976名、2080名、2133名和6058名参与者。在NHANES、WCHAT和WCNPCS中，较高的血清TT始终与BA加速减弱相关。在UKB中，允许使用负数的Box-Cox（BCN）转换后的相对TT变化与BCN转换后的BA加速变化减少显著相关（β：-0.047，95%CI：-0.057至-0.038）。在分层分析、受限立方样条回归（RCS）和敏感性分析中，结果仍然稳健。ADT前后配对检验进一步表明，TT的剥夺加速了前列腺癌患者的生物学衰老。
本研究表明，较高的血清TT与生物衰老的减轻有关。重复检测时血清TT升高的男性BA加速降低。对前列腺癌男性的比较显示，接受ADT后BA加速进展。本研究表明，TT可能是生物衰老的一个合理指标。
中国国家重点研发计划、四川省科技厅项目、国家老年医学临床研究中心、四川大学华西医院。
