Table 1.
Roles of tRNA-modifying enzymes in aging and lifespan.
| tRNA-modifying enzymes | Subjects | Function | Effects | Mechanisms | References |
|---|---|---|---|---|---|
| ALKBH8 | MEFs | Anti-aging | ALKBH8-deficient MEFs showed a senescence phenotype | Characterized by increased levels of SA-β-Gal, HCF, p16INK4a, and SASP markers | 41 |
| dTrm7_34 and dTrm7_32 | Drosophila | Anti-aging | dTrm7_34 and dTrm7_32 mutant flies displayed reduced lifespan | – | 42 |
| mttu-1 and mtcu-2 | C. elegans | Pro-aging | The lifespan of mtcu-2 and mttu-1 double mutants was significantly extended | Associated with OXPHOS dysfunction | 44 |
| Trm9 | Yeast | Pro-aging | Trm9 deletion extended lifespan | Enhanced heat-shock resistance of mutants | 45 |
| hTRM9L | Cancer tissues | Pro-aging | Inhibited tumor growth via a senescence-like arrest | Related to SA-β-Gal activity and p21 expression | 46 |
| NSun2 | Human fibroblasts | Anti-aging | Delayed the process of replicative senescence | Inhibited the translation of p27 by methylating p27 mRNA | 48 |
| NSun2 | Human vascular endothelial cells | Pro-aging | Facilitated premature senescence induced by oxidative stress or high glucose | Promoted the translation of Shc adapter proteins by methylating Shc mRNA, thus activating p38MAPK and increasing ROS production | 49 |
| Dnmt2 | Drosophila | Anti-aging | Dnmt2 was indispensable for maintaining the normal lifespan, and its overexpression prolonged lifespan | – | 52 |
| Dnmt2 | Mouse fibroblasts | Anti-aging | Dnmt2 knockdown fibroblasts were susceptible to senescence under control conditions | Manifested by increased levels of p53 and p21, telomere shortening, oxidative stress and DNA damage | 53 |
| Dnmt2 | Human fibroblasts | Anti-aging | Dnmt2 silencing induced cellular senescence | – | 54 |
tRNA transfer RNA, ALKBH8 alkylation repair homolog 8, MEFs mouse embryonic fibroblasts, SA-β-Gal senescence-associated β-galactosidase, HCF heterochromatin foci, SASP senescence-associated secretory phenotype, OXPHOS oxidative phosphorylation, Trm9 tRNA methyltransferase 9, hTRM9L human Trm9-like protein, NSun2 NOP2/Sun domain family member 2, Shc Src homology and collagen, p38MAPK p38 mitogen-activated protein kinase, ROS reactive oxygen species, Dnmt2 DNA methyltransferase-2.