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Updated: May 27, 2026

Lipid Supplementation for Longevity and Gene Transcriptional Analysis in Caenorhabditis elegans
Published on: December 9, 2022
Phenylalanyl-tRNA synthetase FARS-1/FARSA balances longevity and immunity by downregulating endogenous mitochondrial
Jooyeon Sohn1, Moonhyeon Jeon2, Hanseul Lee1
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, South Korea.
Abstract:
Endogenous double-stranded RNAs (dsRNAs) are immunogenic self-molecules that drive aberrant immune activation under pathological conditions. Here, we show that dsRNAs and their regulation by RNA-binding proteins are key determinants of the fine balance between aging and immunity in Caenorhabditis elegans and cultured human cells. We find elevated levels of dsRNAs with organismal aging and cellular senescence. We identify a moonlighting function for phenylalanyl-tRNA synthetase, FARS-1/FARSA, as a key factor necessary and sufficient for extending lifespan by downregulating dsRNAs, in particular, mitochondrial dsRNAs. FARS-1/FARSA possesses a previously unrecognized dsRNA-binding domain and mediates dsRNA downregulation with the RNA helicase, RHA-2/DHX37, independently of its canonical role in translation. Notably, increased dsRNA expression resulting from genetic inhibition of fars-1/FARSA upregulates immune response-related genes and enhances innate immunity against pathogens. Our study establishes that FARS-1/FARSA is an evolutionarily conserved dsRNA-binding protein that delays aging and promotes longevity by suppressing dsRNA accumulation.
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