A human tissue-specific transcriptomic analysis reveals a complex relationship between aging, cancer, and cellular senescence.

Abstract

Aging is the biggest risk factor for cancer, but the mechanisms linking these two processes remain unclear. Using GTEx and TCGA data, we compared genes differentially expressed with age and genes differentially expressed in cancer among nine human tissues. In most tissues, aging and cancer gene expression pattern changed in the opposite direction. The exception was thyroid and uterus, where we found transcriptomic changes in the same direction in aging and in their corresponding cancers. The overlapping sets between genes differentially expressed with age and genes differentially expressed in cancer across tissues were enriched for several processes, mainly cell cycle and the immune system. Moreover, cellular senescence signatures, derived from a meta-analysis, changed in the same direction as aging in human tissues and in the opposite direction of cancer signatures. Therefore, transcriptomic changes in aging and in cellular senescence might relate to a decrease in cell proliferation, while cancer transcriptomic changes shift toward enhanced cell division. Our results highlight the complex relationship between aging and cancer and suggest that, while in general aging processes might be opposite to cancer, the transcriptomic links between human aging and cancer are tissue-specific.