The NMD complex, which consists of multiple protein components, detects and degrades aberrant transcripts, such as mRNAs containing premature termination codons (PTCs) 11. Nonsense-mediated mRNA decay (NMD) is a key pathway for maintenance of RNA quality. However, whether RNA quality control affects aging is largely unknown.
In addition, proper RNA splicing is crucial for longevity 9, 10. Regarding RNA, several neurodegenerative disorders are associated with defects in RNA-binding protein function 4, 5, and many non-coding RNAs, such as microRNAs and long non-coding RNAs, play regulatory roles in longevity 6, 7, 8. In addition, mutations of somatic DNA and proteotoxicity caused by the accumulation of misfolded proteins underlie normal aging, and proteostasis is an important component of longevity mechanisms 2, 3. For example, accumulation of DNA damage is linked to age-related neurodegenerative diseases and premature aging, including Werner syndrome 1, while disruption of protein homoeostasis is also closely associated with age-related diseases, including Alzheimer’s disease and Parkinson’s disease 2. Deterioration of DNA and protein quality control plays a central role in aging and age-related diseases. We propose that NMD-mediated RNA surveillance is a crucial quality control process that contributes to longevity conferred by daf-2 mutations.Ī key characteristic of aging is a gradual decline in the quality control of biological system components. Furthermore, we find that downregulation of yars-2/tyrosyl-tRNA synthetase, an NMD target transcript, by daf-2 mutations contributes to longevity. NMD in the nervous system of the animals is particularly important for RNA quality control to promote longevity. NMD components, including smg-2/UPF1, are required to achieve the longevity of several long-lived mutants, including daf-2 mutant worms. We find that daf-2 mutants display enhanced NMD activity and reduced levels of potentially aberrant transcripts. elegans strains with mutations in daf-2/insulin/insulin-like growth factor 1 receptor. Here we show that NMD mediates longevity in C. However, whether RNA quality control mechanisms, such as nonsense-mediated mRNA decay (NMD), which degrades both abnormal as well as some normal transcripts, have a role in organismal aging remains unexplored. Long-lived organisms often feature more stringent protein and DNA quality control.
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