Human Peripheral Blood Leukocyte Transcriptome-Based Aging Clock Reveals Acceleration of Aging by Bacterial or Viral Infections

Abstract The aging of the population is a global concern. In the post-coronavirus disease 2019 (COVID-19) pandemic era, there are no effective methods to identify aging acceleration due to infection. In this study, we conducted whole-transcriptome sequencing on peripheral blood samples from 35 healthy individuals (22–88 years old). By analyzing the changes in mRNA, lncRNA, and miRNA expression, we investigated the characteristics of transcriptome alterations during the aging process. ceRNA networks were constructed, and 10 genes (CD248, PHGDH, SFXN2, MXRA8, NOG, TTC24, PHYKPL, CACHD1, BPGM, and TWF1) were identified as potential aging markers and used to construct an aging clock. Moreover, our aging clock categorized individuals into slow-, average-, and quick-aging groups, highlighting a link between accelerated aging and infection-related clinical parameters. Pseudotime analysis further revealed 2 distinct aging trajectories, corroborating the variations in the aging rate identified by the aging clock. Furthermore, we validated the results using the OEP001041 data set (277 healthy individuals aged 17–75), and data sets comprising patients with infectious diseases (n = 1 558). Our study revealed that infection accelerates aging via increased inflammation and oxidative stress in infectious disease patients. Besides, the aging clock exhibited alterations after infection, highlighting its potential for assessing the aging rate after patient recovery. In conclusion, our study introduces a novel aging clock to assess the aging rate in healthy individuals and those with infections, revealing a strong link between accelerated aging and infections through inflammation and oxidative stress. These findings offer valuable insights into aging mechanisms and potential strategies for healthy aging.