Dysregulated RNA processing and metabolism: a new hallmark of ageing and provocation for cellular senescence.

Abstract

The human genome is capable of producing hundreds of thousands of different proteins and non-coding RNAs from <20 000 genes, in a co-ordinated and regulated fashion. This is achieved by a collection of phenomena known as mRNA processing and metabolism, and encompasses events in the life cycle of an RNA from synthesis to degradation. These factors are critical determinants of cellular adaptability and plasticity, which allows the cell to adjust its transcriptomic output in response to its internal and external environment. Evidence is building that dysfunctional RNA processing and metabolism may be a key contributor to the development of cellular senescence. Senescent cells by definition have exited cell cycle, but have gained functional features such as the secretion of the senescence-associated secretory phenotype (SASP), a known driver of chronic disease and perhaps even ageing itself. In this review, I will outline the impact of dysregulated mRNA processing and metabolism on senescence and ageing at the level of genes, cells and systems, and describe the mechanisms by which progressive deterioration in these processes may impact senescence and organismal ageing. Finally, I will present the evidence implicating this important process as a new hallmark of ageing, which could be harnessed in the future to develop new senotherapeutic interventions for chronic disease.