The Significance of 8-oxoGsn in Aging-Related Diseases

Abstract

Aging is a common risk factor for the occurrence and development of many diseases, such as Parkinson's disease, Alzheimer's disease, diabetes, hypertension, atherosclerosis and coronary heart disease, and cancer, among others, and is a key problem threatening the health and life expectancy of the elderly. Oxidative damage is an important mechanism involved in aging. The latest discovery pertaining to oxidative damage is that 8-oxoGsn (8-oxo-7,8-dihydroguanosine), an oxidative damage product of RNA, can represent the level of oxidative stress. The significance of RNA oxidative damage to aging has not been fully explained, but the relationship between the accumulation of 8-oxoGsn, a marker of RNA oxidative damage, and the occurrence of diseases has been confirmed in many aging-related diseases. Studying the aging mechanism, monitoring the aging level of the body and exploring the corresponding countermeasures are of great significance for achieving healthy aging and promoting public health and social development. This article reviews the progress of research on 8-oxoGsn in aging-related diseases.

Keywords: 8-oxoGsn; RNA oxidative damage; aging-related diseases.

Figure 1.

The formation of 8-oxo(d)Gsn. (Up panel) Deoxyguanine (dG) in double-stranded DNA becomes 8-oxodG(GO) under oxidative stress. At this time, 8-oxodG can be directly removed by OGG, or during DNA replication, 8-oxodG is paired with adenine (A) instead of cytosine (C), MYH excision of A is paired with 8-oxodG, and then OGG excision of 8oxodG occurs. (Botton panel) During DNA transcription, G becomes 8-oxoG under oxidative stress, and 8-oxoG is specifically bound and degraded by Y-box binding protein-1 and PNP. The removed 8-oxo(d)G is transformed into 8-oxo(d)Gsn by MTH1, MTH2, NUDT5, and NUDT8 and then enters into tissues, cerebrospinal fluid, blood and urine.