Table 2.
Roles of ARSs in aging and lifespan.
| ARSs | Subjects | Function | Effects | Mechanisms | References |
|---|---|---|---|---|---|
| LARS2 | C. elegans | Pro-aging | A null mutation in LARS2 was associated with longevity | Associated with impaired mitochondrial functions, manifested by lower ATP content and oxygen consumption | 56 |
| LARS | C. elegans | Pro-aging | MML-1/MXL-2 promoted longevity | MML-1/MXL-2 inhibited TOR activity by down-regulating LARS, leading to the nuclear localization and activation of HLH-30/TFEB | 57 |
| LARS | Mouse | Anti-aging | PHD1 levels were reduced in aging muscles, and PHD1 knockout mice had lower muscle mass | PHD1 increased the stability of LARS, thereby ensuring leucine-mediated mTORC1 activation | 58 |
| GARS | Drosophila | Anti-aging | GARS mutations shortened the lifespan of flies in a dosage-dependent manner | Associated with impaired protein synthesis | 59 |
| Aats-met | Drosophila | Anti-aging | Aats-met mutations caused photoreceptor degeneration and reduced lifespan | Associated with increased ROS, oxidative phosphorylation defects and upregulation of mitochondrial unfolded protein response | 61 |
| MARS | Drosophila | Anti-aging | MARS inhibition shortened the lifespan of flies | Reduced the expression of AMPs genes | 62 |
| EPRS | Mouse | Pro-aging | Homozygous EPRS S999A mice exhibited low body weight, reduced adipose tissue mass and increased lifespan | mTORC1-S6K1 phosphorylated EPRS and induced its release from the MSC. Then, the EPRS bound to FATP1 to promote its translocation to the plasma membrane | 63 |
| SerRS | Cancer cells | Pro-aging | Induced cellular senescence | SerRS bound to telomere DNA repeats and enriched POT1 proteins to telomeres, leading to the shortening of telomeres | 64 |
| yars-2 | C. elegans | Pro-aging | NMD-mediated RNA quality control was crucial for longevity | The down-regulation of yars-2, an NMD target, extended the lifespan of mutants | 65 |
| AIMP2 | Mouse | Pro-aging | Contributed to the development of PD | Overexpression of AIMP2 activated PARP1, thereby resulting in an age-dependent dopaminergic neuronal loss | 67 |
| AIMP2-DX2 | Cancer cells | Anti-aging | Blocked oncogene-induced apoptosis and senescence | Inhibited p14/ARF | 68 |
| AIMP3 | Mouse | Pro-aging | AIMP3 levels were increased in aging human tissues, and AIMP3 transgenic mice had a premature aging phenotype | AIMP3 interacted with lamin A and recruited Siah1, which led to the degradation of lamin A and an imbalance in its isoform levels | 69 |
| AIMP3 | hMSCs | Pro-aging | AIMP3 levels were increased, while the levels of miR-543 and miR-590-3p were decreased during the senescence of hMSCs | The two miRNAs inhibited the expression of AIMP3 by binding to AIMP3 transcripts | 70 |
| TyrRS | Mouse | Anti-aging | Mediated the lifespan extension regulated by resveratrol | Resveratrol bound to TyrRS and facilitated its nuclear translocation. Then, TyrRS interacted with PARP1 and promoted its activation | 94 |
| AIMP3 | Mesenchymal stem cells | Pro-aging | AIMP3 down-regulation improved the age-related senescence of stem cells | HIF1α activated autophagy and inhibited mitochondrial respiration via suppressing the expression of AIMP3 | 95 |
ARSs aminoacyl-tRNA synthetases, LARS2 leucyl-tRNA synthetase 2, MML-1/MXL-2 Mondo/Max-like complex, TOR target of rapamycin, PHD1 prolyl-hydroxylase domain protein 1, GARS glycyl-tRNA synthetase, ROS reactive oxygen species, MARS methionyl-tRNA synthetase, AMPs anti-microbial peptides, EPRS glutamyl-prolyl-tRNA synthetase, S6K1 S6 kinase 1, MSC multi-tRNA synthetase complex, FATP1 fatty acid transport protein 1, SerRS seryl-tRNA synthetase, POT1 Protection of Telomeres 1, NMD nonsense-mediated mRNA decay, AIMP2 ARS-interacting multi-functional protein 2, PD Parkinson’s disease, PARP1 poly(ADP-ribose) polymerase-1, AIMP2-DX2 AIMP2 lacking exon 2, Siah1 seven in absentia homolog 1, hMSCs human mesenchymal stem cells, TyrRS tyrosyl-tRNA synthetase, HIF1α hypoxia-inducible factor 1α.