Hallmark of aging
Splicing Dysregulation
Last updated 2026-07-02· Last reviewed 2026-07-02· 1 min read
Reviewed by the Ultimate Longevity Bible editorial team. Educational reference — not medical advice. See disclaimer.
What it is
Splicing dysregulation refers to the age-associated decline in the fidelity and regulation of pre-mRNA splicing — the process by which introns are excised and exons joined to produce mature mRNA. With age, the spliceosome loses precision, and the transcriptome shifts toward aberrant isoforms.
Why it matters for longevity
- Cross-cutting driver: mis-spliced transcripts affect proteins in every hallmark of aging — proteostasis (via mis-folded isoforms), mitochondrial function (via aberrant mitochondrial ribosomal components), and DNA repair (via truncated repair-factor isoforms).
- Disease coupling: aberrant splicing of
TAU,APOE,LMNA, and cardiac troponin isoforms is implicated in Alzheimer's, cardiovascular disease, and progeroid syndromes. - Actionable target: small-molecule splicing modulators (e.g. risdiplam-class drugs) prove that splicing can be pharmacologically redirected — an approach the longevity field is beginning to explore.
Evidence status
Observational human-tissue data is consistent and rapidly expanding (GTEx, Human Cell Atlas). Interventional data in humans is scarce; best mechanistic evidence in worm and mouse models. Candidate-hallmark status likely to formalise this decade.
- Altered Extracellular Matrix — Hallmark.
- Mechanical Aging — Hallmark.
- Metaflammation — Hallmark.
- Turn Biotechnologies — Company.
Related entries
Cellular senescence, Loss of proteostasis, Epigenetic alterations.