The splicing axis of aging: mechanisms and therapeutic opportunities.

Authors

Sada Raza, Ankita Kumari, Maciej Cieśla

Published in

Trends in molecular medicine. Sep 21, 2026. Epub Sep 21, 2026.

Abstract

Aging is characterized by progressive loss of molecular fidelity that compromises stem-cell function and tissue homeostasis. Aging transcriptomes show widespread disruption of RNA processing, including increased intron retention, cryptic splice-site usage, and altered RNA quality control. These changes arise from somatic mutations as well as accumulated transcriptional, metabolic, and proteostatic stress. Importantly, similar splicing abnormalities are observed in age-associated diseases such as clonal hematopoiesis and neurodegeneration, overlapping with physiological aging states. Here, we synthesize mechanistic, stem-cell, and longevity studies to define declining RNA-processing fidelity as a unifying contributor to aging across systems. We propose the 'splicing axis of aging' as a framework linking RNA-processing dysfunction to tissue decline and outline emerging therapeutic strategies to restore spliceosome integrity and RNA homeostasis.

PMID:
42767865
Bibliographic data and abstract were imported from PubMed on 22 Sep 2026.

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