Data from: Transcriptomic alterations during ageing reflect the shift from cancer to degenerative diseases in the elderly

Disease epidemiology during ageing shows a transition from cancer to degenerative chronic disorders as dominant contributors to mortality in the old. Nevertheless, it has remained unclear to what extent molecular signatures of ageing reflect this phenomenon. Here we report on the identification of a conserved transcriptomic signature of ageing based on gene expression data from four vertebrate species across four tissues. We find that ageing-associated transcriptomic changes follow trajectories similar to the transcriptional alterations observed in degenerative ageing diseases but are in opposite direction to the transcriptomic alterations observed in cancer. We confirm the existence of a similar antagonism on the genomic level, where a majority of shared risk alleles that increase the risk of cancer decrease the risk of chronic degenerative disorders and vice versa. These results reveal a fundamental trade-off between cancer and degenerative ageing diseases that sheds light on the pronounced shift in their epidemiology during ageing.

衰老过程中的疾病流行病学呈现出如下转变：老年群体的主要死亡诱因从癌症转向退行性慢性疾病。然而，目前仍不明确衰老的分子特征（molecular signatures）在多大程度上反映了这一流行病学转变。本研究基于四类脊椎动物的四种组织的基因表达数据，成功鉴定出了进化保守的衰老转录组特征（transcriptomic signature）。研究发现，衰老相关的转录组变化轨迹与退行性衰老疾病中的转录改变轨迹相似，但与癌症中的转录组改变方向完全相反。我们在基因组水平上验证了类似的拮抗作用：大多数可增加癌症发病风险的共有风险等位基因（risk alleles），会降低慢性退行性疾病的发病风险，反之亦然。上述研究结果揭示了癌症与退行性衰老疾病之间存在根本性的权衡关系，这一发现阐明了二者在衰老过程中流行病学特征的显著转变。