An integrated resource for systems-level analysis of aging hallmarks and associated genes

AgingHallmarksDB is an interactive web platform designed to facilitate systems-level aging research centered on 11 aging hallmarks. It comprises 3111 aging hallmark-associated genes integrated from seven established databases, including a high-confidence consensus set comprising 1089 genes. It further incorporates tissue, cell-type class, exosomes, protein-protein and regulatory interactions to facilitate deeper biological insights. AgingHallmarksDB enables over representation analysis (ORA) and gene set enrichment analysis (GSEA) to elucidate varying molecular mechanisms underlying aging. Gene overlaps and Jaccard similarity revealed interconnectedness among the hallmarks. Network analyses further showed these pairs are connected within the protein-protein interaction (PPI) network. The utility of this resource was demonstrated through multiple hallmark-associated analyses. PPI network topology analysis of common hallmark genes revealed several key age-associated genes that act as central hubs across multiple aging hallmarks. Hallmark enrichment analyses revealed extensive coverage across aging-related diseases compared to limited enrichment seen in non-aging-related diseases like developmental and congenital diseases. Further these analyses showed biologically meaningful disease-associated processes, like "Loss of proteostasis" in Alzheimer's disease and "Chronic inflammation" in atherosclerosis as highly significant hallmarks. These disease-hallmark associations were further supported by network proximity analyses. In addition, GSEA of the PM2.5 exposure-associated skin transcriptome identified significant enrichment of aging hallmarks, particularly "Epigenetic alterations", demonstrating the resource's utility in interpreting transcriptomic datasets within the context of aging biology. Overall, AgingHallmarksDB provides a robust framework for investigating hallmark-associated functionality, and potential therapeutic discovery in aging and longevity. AgingHallmarksDB is accessible at https://cb.imsc.res.in/aginghallmarksdb/ .