Anti-aging Effects of Alu Antisense RNA on Human Fibroblast Senescence Through the MEK-ERK Pathway Mediated by KIF15
Ning Ji1, Chong-Guang Wu1, Xiao-Die Wang1
1Department of Genetics, Hebei Medical University, Hebei Key Lab of Laboratory Animal, Shijiazhuang, 050017, China.
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.
Insights
Human short interspersed nuclear element antisense RNA (Alu asRNA) delays fibroblast aging by activating the KIF15-mediated MEK-ERK pathway, promoting cell proliferation. This finding offers potential therapeutic strategies for aging-related conditions.
Area of Science:
- Molecular Biology
- Cell Biology
- Aging Research
Background:
- Cellular senescence is a key factor in aging.
- Human short interspersed nuclear element antisense RNA (Alu asRNA) is a non-coding RNA with potential regulatory functions.
- Investigating novel regulators of senescence is crucial for understanding aging mechanisms.
Purpose of the Study:
- To determine if Alu asRNA can delay human fibroblast senescence.
- To elucidate the underlying molecular mechanisms of Alu asRNA's effect on aging.
- To explore the role of KIF15 in Alu asRNA-mediated anti-aging effects.
Main Methods:
- Senescent human fibroblasts were transfected with Alu asRNA.
- Cell Counting Kit-8 (CCK-8), reactive oxygen species (ROS) assays, and SA-β-gal staining were used to assess anti-aging effects.
- RNA-sequencing (RNA-seq) and KEGG pathway analysis identified differentially expressed genes and enriched pathways.
- KIF15 expression and MEK-ERK signaling pathway activation were examined.
Main Results:
- Alu asRNA transfection delayed fibroblast aging, as evidenced by CCK-8, ROS, and SA-β-gal assays.
- RNA-seq revealed 183 differentially expressed genes, with significant enrichment in the cell cycle pathway.
- Alu asRNA significantly upregulated KIF15 expression and activated the MEK-ERK signaling pathway.
Conclusions:
- Alu asRNA demonstrates anti-aging properties by delaying fibroblast senescence.
- The anti-aging effect is mediated through the KIF15-dependent activation of the MEK-ERK signaling pathway.
- Alu asRNA promotes senescent fibroblast proliferation, suggesting a potential therapeutic target for aging.
