The Multidimensional System Biology Analysis of Cellular Senescence and Ageing
Cellular senescence is the hallmark of ageing, and it has been associated with age-related diseases such as cancer. Senescent cells accumulate in the tissues of old organisms, which can cause chronic inflammation. Cell senescence is associated with many genes, but a complete understanding of the cell senescence pathway still remains elusive. 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 found that genes that promote cell senescence are overexpressed in tissues of older humans and also overrepresented in databases for anti-aging and tumour suppressor genes. Genes inhibiting cell-senescence overlapping with prolongation genes and oncogenes. Furthermore, an evolutionary analysis revealed a strong conservation of senescence-associated genes in mammals, but not in invertebrates. We also constructed protein-protein interactions and coexpression networks using the CellAge gene as seed nodes. The clusters of the networks were more enriched in cell cycle and immune processes. Network topological parameters also revealed novel potential senescence-associated regulators. Then, we used siRNAs to observe that 19 of the 26 candidates tested induced markers for senescence. Our work offers researchers a new tool to study cell death and our systems-biology analyses have revealed novel genes and new insights about cell senescence.