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.

A multidimensional systems biology analysis of cellular senescence in aging and disease

“…A total of 1240 differentially expressed signatures of CS were also overlapped with the GTEx aging DEGs in 26 human tissues, including 9 tissues previously analyzed ( Fig. 2b) [32]. The overexpressed signatures of CS were significantly overexpressed across multiple tissues with age, and only significantly underexpressed with age in the brain and uterus (p < 0.05, Fisher's exact test with BH correction) (Additional file 1: Table S13).…”

“…Then, we examined the differential expression of CS genes with age in different tissues. Using a previously generated gene set of differentially expressed genes (DEGs) with age in 26 tissues on GTEx [32,43], we found overlaps with 268 CellAge inducers and inhibitors of CS present in the gene expression data (Fig. 2a).…”

“…We have also performed a meta-analysis to derive a molecular signature of replicative CS and found 526 overexpressed and 734 underexpressed genes [32]. These gene signatures are also available on the CellAge website.…”

“…The Genotype-Tissue Expression (GTEx) project contains expression data from 53 different tissue sites collected from 714 donors ranging from 20 to 79 years of age, grouped into 26 tissue classes [43]. We asked if CellAge genes and differentially expressed signatures of CS were expressed in a tissue-specific manner [42] and determined how CS gene expression changes across different tissues with age [32].…”

Positive selection and gene duplications in tumour suppressor genes reveal clues about how cetaceans resist cancer

“…Ageing is the biggest risk factor for developing cancer and is characterized by the progressive accumulation of cellular damage, but the mechanisms linking these two processes -ageing and cancer-remain unclear 46 . One of the mechanisms that define how well we age, is the regulation of energy flow in the cells 47 .…”