Mechanistic Insights Into 5′‐ <scp>tiRNA</scp> ‐His‐ <scp>GTG</scp> Mediated Activation of the <scp>JNK</scp> Pathway in Skin Photoaging

UV exposure leads to skin damage, thus inducing skin aging. The aims of this study were to explore the differences in tRNA-derived small RNAs (tsRNAs) expression in the Human dermal fibroblasts (HDF cells) photoaging cell model and to explore the biological functions of tsRNA in skin photoaging. In this study, we found that in both photoaging cell models and the skin of photoaging mice, the 5'-tiRNA-His-GTG expression levels were significantly elevated. In HDF cells, overexpression of 5'-tiRNA-His-GTG induces cellular senescence. Inhibition of 5'-tiRNA-His-GTG attenuates UVB-induced cellular senescence in the photoaging cell model. Intradermal injection of Adeno-associated virus 9-5'-tiRNA-His-GTG -Inhibition ameliorates UVB-induced skin photoaging in nude mice. We confirmed that 5'-tiRNA-His-GTG targeted nuclear pore proteins 98, which further activated the JNK signaling pathway and induced cell senescence. Targeting 5'-tiRNA-His-GTG may provide a novel therapeutic option for ameliorating skin photoaging.