Optimized primer and model improve precision of X chromosome telomere length determination in the Han population

The attrition of telomere length is associated with cellular aging and plays a role in multiple age-related disorders. This study analyzed the relationship between telomere length on the X chromosome and age in the Han population (<i>n</i> = 492) using whole-genome sequencing and long-read sequencing data from 32 individuals. We developed three pairs of primers and completed measurements in a cohort of 124 individuals. We then constructed an online prediction tool based on a three-layer feedforward neural network and validated its performance in an independent cohort of 41 individuals. Our results revealed a complex association between X chromosome telomere length and aging. No significant changes were observed in individuals under 30, while a significant negative correlation emerged in the population over 40, suggesting a potential "telomere shortening accelerating point (TSAP)" around this age. This finding challenges the conventional view of linear telomere shortening, and our model provides effective tools for exploring aging mechanisms.