Loss of Splicing Homeostasis as a Hallmark of Aging - PubMed
5 hours ago
- #Senescence
- #RNA Splicing
- #Aging
- Alternative splicing is crucial for gene expression, cellular adaptability, and protein diversity.
- Aging leads to weakened splicing fidelity, disrupting RNA homeostasis and essential cellular functions.
- Splicing defects are linked to mitochondrial dysfunction, genome instability, and immune dysregulation.
- Senescent cells and aged tissues show altered splicing factors and increased RNA polymerase II elongation rates.
- Mis-spliced isoforms contribute to senescence and age-related diseases like Alzheimer's and Parkinson's.
- RNA-binding protein dysfunction exacerbates aberrant splicing in aging.
- Therapeutic strategies include antisense oligonucleotides, RNA interference, CRISPR-Cas, and RNA aptamers.
- Challenges include distinguishing pathological splicing noise and achieving targeted delivery.
- Restoring splicing homeostasis could extend health span by stabilizing transcriptomic programs.