The STAT3 Paradox in Aging: Molecular Mechanisms and Targeted Therapeutic Strategies - PubMed

3 days ago

STAT3 plays dual roles in aging, both promoting and inhibiting senescence.
Key posttranslational modifications (PTMs) like phosphorylation (Y705, S727), acetylation, and methylation regulate STAT3 activity and localization.
Y705 phosphorylation of STAT3 mainly promotes aging by driving inflammation, fibrosis, and mitochondrial dysfunction.
S727 phosphorylation of STAT3 has potential anti-aging effects by maintaining stem cell properties and tissue regeneration.
Other PTMs such as sulphenylation and O-GlcNAcylation also influence STAT3-mediated aging processes.
The paradoxical roles of STAT3 are due to cellular/tissue specificity, signaling crosstalk, and temporal activation dynamics.
Potential anti-aging strategies targeting STAT3 include small-molecule inhibitors, natural compounds, epigenetic modulators, and gene-based therapies.
Understanding context-dependent STAT3 signaling and precise targeting of PTMs is crucial for developing effective anti-aging therapies.

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