Age-related but not longevity-related genes are found by weighted gene co-expression network analysis in the peripheral blood cells of humans

Human lifespan is determined by genetic and environmental factors. Potential longevity genes are neither specific nor reproducible, and longevity-related genes are constantly confused with age-related genes. To distinguish specific age- and longevity-related genes, we analyzed a Gene Expression Omnibus (GEO) dataset established by the Leiden Longevity Study. The individuals were classified into longevity (mean age, 93.4 ± 3.0 years), longevity offspring (60.8 ± 6.1) and control (61.9 ± 6.9) groups. The series matrix files were downloaded, and average expression values were calculated. Differentially expressed genes (DEGs) between longevity and control groups and those between longevity and their offspring were identified by GEO2R online. A total of 507 longevity- and 755 age-related DEGs were visualized using a Venn diagram. Weighted gene co-expression network analysis (WGCNA) was performed on the longevity- and age-related DEGs. Age-related color modules and genes were identified. However, no longevity-related modules or genes were found. The green module, with 46 age-related DEGs, was the most biologically significant to age and aging. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction pathway analyses were conducted on these 46 DEGs, which are mainly enriched in B cell activation and receptor signaling pathways. CR2, VPREB3, MS4A1 and CCR6 were considered the most crucial candidate genes for aging.