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. 2023 Feb 20;43(1):35–47. doi: 10.1007/s11596-022-2688-z

Anti-aging Effects of Alu Antisense RNA on Human Fibroblast Senescence Through the MEK-ERK Pathway Mediated by KIF15

Ning Ji 1, Chong-guang Wu 1, Xiao-die Wang 1, Zhi-xue Song 1, Pei-yuan Wu 1, Xin Liu 1, Xu Feng 1, Xiang-mei Zhang 2, Xiu-fang Wang 1,✉, Zhan-jun Lv 1,✉
PMCID: PMC9939868  PMID: 36808398

Abstract

Objective

To investigate whether human short interspersed nuclear element antisense RNA (Alu antisense RNA; Alu asRNA) could delay human fibroblast senescence and explore the underlying mechanisms.

Methods

We transfected Alu asRNA into senescent human fibroblasts and used cell counting kit-8 (CCK-8), reactive oxygen species (ROS), and senescence-associated beta-galactosidase (SA-β-gal) staining methods to analyze the anti-aging effects of Alu asRNA on the fibroblasts. We also used an RNA-sequencing (RNA-seq) method to investigate the Alu asRNA-specific mechanisms of anti-aging. We examined the effects of KIF15 on the anti-aging role induced by Alu asRNA. We also investigated the mechanisms underlying a KIF15-induced proliferation of senescent human fibroblasts.

Results

The CCK-8, ROS and SA-β-gal results showed that Alu asRNA could delay fibroblast aging. RNA-seq showed 183 differentially expressed genes (DEGs) in Alu asRNA transfected fibroblasts compared with fibroblasts transfected with the calcium phosphate transfection (CPT) reagent. The KEGG analysis showed that the cell cycle pathway was significantly enriched in the DEGs in fibroblasts transfected with Alu asRNA compared with fibroblasts transfected with the CPT reagent. Notably, Alu asRNA promoted the KIF15 expression and activated the MEK-ERK signaling pathway.

Conclusion

Our results suggest that Alu asRNA could promote senescent fibroblast proliferation via activation of the KIF15-mediated MEK-ERK signaling pathway.

Electronic supplementary material

The online version of this article (10.1007/s11596-022-2688-z) contains supplementary material, which is available to authorized users.

Key words: senescent fibroblast, cell proliferation, Alu antisense RNA, KIF15 gene expression, MEK-ERK signaling pathway, cell cycle

Supplementary data

11596_2022_2688_MOESM1_ESM.pdf (390.5KB, pdf)

Supplementary material, approximately 390 KB.

Conflict of Interest Statement

The authors declare no conflicts of interests related to this study.

Footnotes

This work was supported by grants from the National Natural Science Foundation of China (No. 81771499) and the Natural Science Foundation of Hebei Province, China (No. H2018206099 and No. H2021206460).

Contributor Information

Ning Ji, Email: 20201011@stu.hebmu.edu.cn.

Xiu-fang Wang, Email: wangxf1966@hebmu.edu.cn.

Zhan-jun Lv, Email: lslab@hebmu.edu.cn.

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