MicroRNA Regulation of Oxidative Stress-Induced Cellular Senescence

Abstract

Aging is a time-related process of functional deterioration at cellular, tissue, organelle, and organismal level that ultimately brings life to end. Cellular senescence, a state of permanent cell growth arrest in response to cellular stress, is believed to be the driver of the aging process and age-related disorders. The free radical theory of aging, referred to as oxidative stress (OS) theory below, is one of the most studied aging promoting mechanisms. In addition, genetics and epigenetics also play large roles in accelerating and/or delaying the onset of aging and aging-related diseases. Among various epigenetic events, microRNAs (miRNAs) turned out to be important players in controlling OS, aging, and cellular senescence. miRNAs can generate rapid and reversible responses and, therefore, are ideal players for mediating an adaptive response against stress through their capacity to fine-tune gene expression. However, the importance of miRNAs in regulating OS in the context of aging and cellular senescence is largely unknown. The purpose of our article is to highlight recent advancements in the regulatory role of miRNAs in OS-induced cellular senescence.

Figure 1

Role of ROS in aging and youthful physiology.

Figure 2

Role and regulation of micro-RNAs in aging and senescence.

Figure 3

MicroRNAs and their mRNA targets as modulators of redox biology, mitochondrial metabolism, and quality control of DNA and proteins. The maintenance of DNA and protein quality is crucial for the preservation of youthful physiology in animals. Accordingly, mechanisms of DNA and protein quality control (QC) were identified as key targets for cellular senescence and aging. The performance of both QC mechanisms is affected by both mitochondrial and cytosolic ROS. Depicted here are known functions of microRNAs as mediators between ROS production and QC mechanisms. The final outcome of this regulatory circuit is further modulated by other (additional) mechanisms which are currently incompletely understood.