Scientists have long strived to understand the aging process in order to combat age-related diseases and attain longevity. However, a complete picture of the inherently complex underpinnings remains ever elusive.
DNA, RNA, and proteins carry the genetic instructions within all known living organisms. Existing research has collectively shown that organisms with long lifespans tend to have more stringent DNA and protein quality control. In other words, deterioration of DNA and protein quality control is centrally correlated with aging and age-related diseases. However, the role of the RNA quality control in aging remained almost unexplored.
Now, research published in the journal Nature Communications shows that RNA quality control affects aging.
The research team concentrated on a specific RNA quality control mechanism called nonsense-mediated mRNA decay (NMD), a key pathway which degrades both abnormal as well as some normal RNAs. The team has successfully shown that NMD is crucial for longevity in the roundworm called C. elegans, a popularly used animal for aging research.
They first discovered that NMD activity decreases during aging. The team then discovered that enhanced NMD underlies the longevity of famous C. elegans strains called daf-2 mutants, which have reduced insulin hormone signaling.
NMD components, including smg-2/UPF1, are required to achieve the longevity of several long-lived mutants, including daf-2 mutant worms. NMD in the nervous system of the animals is particularly important for RNA quality control to promote longevity.
Since the main role of NMD is degradation of its target mRNAs, the team focused on mRNAs that were downregulated in daf-2 mutants. Their research showed substantially decreased levels of a gene yars-2, an NMD target, are at least partially responsible for long lifespan in daf-2 mutants. In other words, research data collectively suggest that NMD-mediated RNA quality control is critical for longevity in C. elegans.
Role of RNA quality control in longevity!
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