Characteristics of Age-Associated Changes in the Whole Transcriptome of Human Peripheral Blood Leukocytes and Establishment of an Aging Clock

In the post-pandemic era, there are limited methods for identifying accelerated aging through peripheral blood transcriptomics. Therefore, we conducted whole-transcriptome sequencing on 35 healthy individuals (22-88 years old). Analyzing mRNA, lncRNA, and miRNA expression, we constructed a ceRNA network and employed a random forest algorithm to develop an aging clock based on 10 genes, validated by pseudo-time analysis and RT-PCR. Utilizing the OEP001041 dataset (277 healthy individuals, aged 17-75) and datasets comprising patients with infectious diseases (n = 1558), we validated the aging clock's ability to categorize the aging rates among different individuals, uncovering associations between aging rates and infectious diseases. Further investigations revealed that infections accelerate aging by elevating inflammation and oxidative stress. Importantly, the aging clock demonstrated alterations post-infection, showcasing its potential in assessing the aging rate after patient recovery. This study uncovers potential factors contributing to accelerated aging and promotes the development of healthy aging. Overall design: We recruited 35 healthy individuals (22-88 years old), referred to as the "BJH cohort," from April 2022 to October 2022 from residential areas in Beijing and the Beijing Hospital Health Examination Center. The individuals were categorized into three age groups: Young (n=11), with an average age of 27.5 (±2.54); Middle (n=10), with an average age of 60.4 (±2.22); and Old (n=14), with an average age of 80.5 (±4.57). Individuals participating in the study had to meet the following criteria: not suffering from major diseases that severely impact physiological functions, such as cancer, stroke, blood disorders, or severe immune abnormalities. Each volunteer underwent a health examination, and 5 mL of peripheral blood was collected. For each blood sample, one portion was collected in a tube containing EDTA for routine clinical blood testing and RNA extraction, while another portion was collected in an additive-free dry vacuum tube for biochemical analysis.