The Potential Role of m6A RNA Methylation in the Aging Process and Aging-Associated Diseases

Abstract

N6-methyladenosine (m6A) is the most common and conserved internal eukaryotic mRNA modification. m6A modification is a dynamic and reversible post-transcriptional regulatory modification, initiated by methylase and removed by RNA demethylase. m6A-binding proteins recognise the m6A modification to regulate gene expression. Recent studies have shown that altered m6A levels and abnormal regulator expression are crucial in the ageing process and the occurrence of age-related diseases. In this review, we summarise some key findings in the field of m6A modification in the ageing process and age-related diseases, including cell senescence, autophagy, inflammation, oxidative stress, DNA damage, tumours, neurodegenerative diseases, diabetes, and cardiovascular diseases (CVDs). We focused on the biological function and potential molecular mechanisms of m6A RNA methylation in ageing and age-related disease progression. We believe that m6A modification may provide a new target for anti-ageing therapies.

Epigenetic regulation of aging: implications for interventions of aging and diseases

“…m 6 A is regulated by writer, reader, and eraser proteins. 152 , 153 The multi-subunit writer RNA methyltransferases (MTases) are assembled mainly by methyltransferase like 3 (METTL3), METTL14, and Wilms tumor 1 associating protein (WTAP). 154 The first reported m 6 A modification involved in senescence is methylation at the 3ʹ-UTR of the CDKN1A mRNAs by a METTL3/14 heterodimer, which facilitates p21 translation.…”

The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence

“…When the DNA damage response (DDR) is prolonged, it promotes senescence [4]. Further known mechanisms underlying senescence are: (1) persistent DDR activation at telomeres, the ends of chromosomes, which is sufficient to activate replicative cell senescence [8]; (2) oncogene activation partly via reactive oxygen species (ROS) production, determining hyperproliferation and altered DNA replication profiles [4,8]; (3) cell cycle arrest by upregulation of p21 and p16 [9]; (4) mitochondrial abnormalities with an increase in ROS synthesis and impairment in biogenesis and mitophagy [10]; (5) induction to resistance to apoptosis by upregulation of the antiapoptotic proteins [10]; (6) metabolic changes determined by senescence-associated-β-galactosidase (SA-β gal) accumulation along with the increase in cellular lysosomal content [10]; (7) large-scale chromatin reorganization occurring with the generation of senescence-associated heterochromatin foci, which suppress transcription of pro-proliferation genes [10]; (8) secretion of pro-inflammatory cytokines, chemokines, proteases, and growth factors that influence the neighbouring cells (SASP profile); (9) morphological alterations including cellular flattening and enlargement [10]; (10) post-transcriptional regulatory pathways taking place at different levels: through the action of mRNA-binding proteins (RBPs) and noncoding RNAs [11][12][13][14]; through a dysregulated splicing factor expression [12,15]; and through N6-methyladenosine (m6A) processes with specific m6A-binding proteins [14].…”

N6-methyladenosine (m6A) RNA modification as a metabolic switch between plant cell survival and death in leaf senescence

“…The research has shown the possibility of the existence of complex senescence regulatory mechanisms including RNA modifications (Sobieszczuk-Nowicka et al, 2018); therefore, investigation of the epigenetic mechanisms participating in leaf senescence is an important research topic. As has already been mentioned the role of m 6 A modifications in the aging of animal models as well as cell senescence has been previously reported (Castro-Hernańdez et al, 2022;Sun et al, 2022b). Recent findings about m 6 A modification in the process of aging include the participation of this modification in cell senescence, inflammation, autophagy, DNA damage, oxidative stress, neurodegenerative diseases, tumors, diabetes, and cardiovascular diseases.…”