Related Experiment Video
Updated: Sep 8, 2026

Sex Stratified Neuronal Cultures to Study Ischemic Cell Death Pathways
Published on: December 9, 2013
Joint Effects of Long-Term Obesity and Genetic Susceptibility on Sex-Specific Brain Aging
Miaomiao Zhu1, Fan Yang1, Jia Guo1,2
1Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
Objective:
This study aimed to examine the associations of longitudinal obesity trajectories and polygenic risk with sex-specific brain aging.
Methods:
We analyzed 35,092 UK Biobank participants (16,484 males and 18,608 females). Sex-specific XGBoost models estimated multimodal brain age. We derived 16-year longitudinal obesity trajectories from repeatedly collected anthropometric measurements. Polygenic risk scores were constructed based on 55 independent genetic loci. Multivariable logistic regression examined associations of obesity trajectories and genetic risk with brain age acceleration.
Results:
A total of 8198 (49.73%) males and 9089 (48.84%) females had accelerated brain aging. High genetic risk significantly increased brain age acceleration odds (males: OR = 1.39; females: OR = 1.34). Crucially, the high-stable obesity trajectory exerted a stronger effect in males (OR = 1.90, 95% CI: 1.64-2.21) than in females (OR = 1.25, 95% CI: 1.12-1.40), with the joint presence of high genetic risk and high-stable obesity amplifying risk to an OR of 2.78 in males and 1.57 in females. Conversely, shifting from obesity to non-obesity reduced risk by 30% in males and 18% in females.
Conclusions:
These findings underscore long-term obesity as a critical, sex-dimorphic driver of accelerated brain aging, and midlife weight management offers robust neuroprotection even in genetically susceptible individuals.
Related Concept Videos
Human Genetics
The complex relationship between genetics and psychology is observable through common biological components such...
Biological Influences on Intelligence
Obesity
Alzheimer Disease l: Introduction
Aging
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
The Effect of Aging on Tissues
