Noncoding RNA control of cellular senescence

Abstract

Senescent cells accumulate in normal tissues with advancing age and arise by long-term culture of primary cells. Senescence develops following exposure to a range of stress-causing agents and broadly influences the physiology and pathology of tissues, organs, and systems in the body. While many proteins are known to control senescence, numerous noncoding (nc)RNAs are also found to promote or repress the senescent phenotype. Here, we review the regulatory ncRNAs (primarily microRNAs and lncRNAs) identified to-date as key modulators of senescence. We highlight the major senescent pathways (p53/p21 and pRB/p16), as well as the senescence-associated secretory phenotype (SASP) and other senescence-associated events governed by ncRNAs, and discuss the importance of understanding comprehensively the ncRNAs implicated in cell senescence.

Figure 1. ncRNAs promoting and inhibiting senescence

Schematic representation of the main microRNAs and lncRNAs that promote (black) or inhibit (white) senescence phenotypes driven by p53/p21 (top left) pRB/p16 (top right), SASP and other mediators (bottom). Center, senescent fibroblasts displaying blue color indicative of SA-β-galactosidase (SA-β-gal) activity.