Zeng Xiaomin, Chen Ruiye, Shi Danli, Zhang Xiayin, Su Ting, Wang Yaxin, Hu Yijun, He Mingguang, Yu Honghua, Shang Xianwen
Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
The Ophthalmic Epidemiology Department, Centre for Eye Research Australia, Melbourne, Victoria, Australia.
Aging Cell. 2025 Apr;24(4):e14435. doi: 10.1111/acel.14435. Epub 2024 Dec 12.
This study aims to investigate the association between metabolomic aging acceleration and body mass index (BMI) phenotypes with mortality and obesity-related morbidities (ORMs). 85,458 participants were included from the UK Biobank. Metabolomic age was determined using 168 metabolites. The Chronological Age-Adjusted Gap was used to define metabolomically younger (MY) or older (MO) status. BMI categories were defined as normal weight, overweight, and obese. Participants were categorized into MY normal weight (MY-NW, reference), MY overweight (MY-OW), MY obesity (MY-OB), MO normal weight (MO-NW), MO overweight (MO-OW), and MO obesity (MO-OB). Mortality and 43 ORMs were identified through death registries and hospitalization records. Compared with MY-NW phenotype, MO-OB phenotype yielded increased risk of mortality and 32 ORMs, followed by MO-OW with mortality and 27 ORMs, MY-OB with mortality and 26 ORMs, MY-OW with 21 ORMs, and MO-NW with mortality and 14 ORMs. Consistently, MO-OB phenotype showed the highest risk of developing obesity-related multimorbidities, followed by MY-OB phenotype, MO-OW phenotype, MY-OW phenotype, and MO-NW phenotype. Additive interactions were found between metabolomic aging acceleration and obesity on CVD-specific mortality and 10 ORMs. Additionally, individuals with metabolomic aging acceleration had higher mortality and cardiovascular risk, even within the same BMI category. These findings suggest that metabolomic aging acceleration could help stratify mortality and ORMs risk across different BMI categories. Weight management should also be extended to individuals with overweight or obesity even in the absence of accelerated metabolomic aging, as they face increased healthy risk compared with MY-NW individuals. Additionally, delaying metabolic aging acceleration is needed for all metabolomically older groups, including those with normal weight.
本研究旨在调查代谢组学衰老加速与体重指数（BMI）表型与死亡率及肥胖相关发病情况（ORMs）之间的关联。研究纳入了英国生物银行的85458名参与者。使用168种代谢物确定代谢组学年龄。采用按时间年龄调整的差距来定义代谢组学上较年轻（MY）或较年长（MO）状态。BMI类别定义为正常体重、超重和肥胖。参与者被分为MY正常体重（MY-NW，参照组）、MY超重（MY-OW）、MY肥胖（MY-OB）、MO正常体重（MO-NW）、MO超重（MO-OW）和MO肥胖（MO-OB）。通过死亡登记和住院记录确定死亡率和43种ORMs。与MY-NW表型相比，MO-OB表型导致死亡率和32种ORMs风险增加，其次是MO-OW导致死亡率和27种ORMs，MY-OB导致死亡率和26种ORMs，MY-OW导致21种ORMs，MO-NW导致死亡率和14种ORMs。一致地，MO-OB表型显示出发生肥胖相关多种疾病的风险最高，其次是MY-OB表型、MO-OW表型、MY-OW表型和MO-NW表型。在代谢组学衰老加速与肥胖之间发现了关于心血管疾病特异性死亡率和10种ORMs的相加相互作用。此外，即使在相同的BMI类别中，代谢组学衰老加速的个体也有更高的死亡率和心血管风险。这些发现表明，代谢组学衰老加速有助于在不同BMI类别中对死亡率和ORMs风险进行分层。体重管理也应扩展到超重或肥胖个体，即使他们没有代谢组学衰老加速，因为与MY-NW个体相比，他们面临的健康风险增加。此外，对于所有代谢组学上较年长的群体，包括体重正常的群体，都需要延缓代谢衰老加速。
