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Cellular senescence, a permanent state of replicative arrest in otherwise proliferating cells, is a hallmark of ageing and has been linked to ageing-related diseases like cancer. Senescent cells have been shown to accumulate in tissues of aged organisms which in turn can lead to chronic inflammation. Many genes have been associated with cell senescence, yet a comprehensive understanding of cell senescence pathways is still lacking. To this end, we created CellAge (http://genomics.senescence.info/cells), a manually curated database of 279 human genes associated with cellular senescence, and performed various integrative and functional analyses. We observed that genes promoting cell senescence tend to be overexpressed with age in human tissues and are also significantly overrepresented in anti-longevity and tumour-suppressor gene databases. By contrast, genes inhibiting cell senescence overlapped with pro-longevity genes and oncogenes. Furthermore, an evolutionary analysis revealed a strong conservation of senescence-associated genes in mammals, but not in invertebrates. Using the CellAge genes as seed nodes, we also built protein-protein interaction and co-expression networks. Clusters in the networks were enriched for cell cycle and immunological processes. Network topological parameters also revealed novel potential senescence-associated regulators. We then used siRNAs and observed that of 26 candidates tested, 19 induced markers of senescence. Overall, our work provides a new resource for researchers to study cell senescence and our systems biology analyses provide new insights and novel genes regarding cell senescence.

In spite of a growing body of research and data, human ageing remains a poorly understood process. To facilitate studies of ageing, over 10 years ago we developed the Human Ageing Genomic Resources (HAGR), which are now the leading online resource for biogerontologists. In this update, we present HAGR’s main functionalities, including new additions and improvements to HAGR. HAGR consists of five databases: 1) the GenAge database of ageing-related genes, in turn composed of a dataset of >300 human ageing-related genes and a dataset with >2000 genes associated with ageing or longevity in model organisms; 2) the AnAge database of animal ageing and longevity, featuring >4000 species; 3) the GenDR database with >200 genes associated with the life-extending effects of dietary restriction; 4) the LongevityMap database of human genetic association studies of longevity with >500 entries; 5) the DrugAge database with >400 ageing or longevity-associated drugs or compounds; 6) the CellAge database with >200 genes associated with cell senescence. All our databases are manually curated by experts to ensure a high quality data and presented in an intuitive and clear interface that includes cross-links across our databases and to external resources. HAGR is freely available online (http://genomics.senescence.info/).