Evidence for RNA Quality Control to be Among the Determinants of Longevity
Cellular quality control mechanisms such as autophagy are observed to be influential in determining natural variations in longevity. Increased autophagy, meaning that cells are working harder to recycle damaged structures and proteins, is a prominent feature of many of the interventions shown to modestly slow aging in laboratory species over the past twenty years. As a further example, autophagy appears to be required for the enhanced health and longevity produced by the practice of calorie restriction. There are other forms of quality control process beyond autophagy, however, and here researchers provide evidence to suggest that those focused on RNA molecules are also important:
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.
Researchers have now shown 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.
Since the main role of NMD is degradation of its target messenger RNAs (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. The researchers anticipate that the discovery of the causal relationship between RNA quality control and longevity will play a significant role in shedding light on the mechanisms behind aging and eventually contribute to curing and even preventing age-related diseases.
Link: https://www.eurekalert.org/pub_releases/2017-03/puos-ral030917.php
Why does NMD activity decrease with age?