Xiao, FH. and Wang, HT. and Zhao, L. and Li, GH. and Ma, SY. and Yang, LQ. and Wang, H. and Zhang, YX. and Li, J. and Kong, QP.
doi:10.1016/j.xcrm.2026.102767
Abstract
A youthful molecular profile reflects attenuated aging and preserved health in advanced age. Long-lived individuals (LLIs) show youthful patterns in DNA methylation and gut microbiota, yet their transcriptional trajectories remain undercharacterized. We analyze transcriptomes from 811 LLIs and 940 younger controls (YCs) to map transcriptional aging trajectories. Clocks trained on YCs reveal that LLIs possess markedly younger transcriptional ages than expected. We identify gene clusters deviating from YC-derived aging trajectories in LLIs, notably eight mitochondrial ribosomal protein genes (mRPGs) resisting typical age-related expression decline. An elevated 8-mRPG expression score correlates with lower aging levels inferred from established aging- and senescence-related gene gets. Samples with higher 8-mRPG scores exhibit increased expression of mitochondrial-function-related genes, including those in aerobic respiration and respiratory electron transport. Together, these findings indicate that the sustained expression of specific mRPGs in LLIs is a signature of attenuated transcriptomic aging that may reflect preserved mitochondrial function.