Neuromolecular medicineJul 17, 2026

STAT6 Controls Cell Cleanup to Affect Brain Immune Cell Aging in Thinking Problems from Small Blood Vessel Disease

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Jul 18, 2026

Abstract

Phosphorylation-mediated STAT6 activation significantly suppressed microglial senescence.

Cerebral small-vessel disease may drive vascular cognitive impairment through cellular senescence and neuroinflammation.
Microglia, the brain's immune cells, are associated with worsening cognitive dysfunction due to their senescence.
STAT6 activation could alleviate neuroinflammation and cognitive deficits related to cerebral small-vessel disease.
Enhanced autophagy, triggered by phosphorylated STAT6, may reduce the burden of senescent microglia.
These processes could lead to improvements in cognitive function in models of vascular cognitive impairment.

Simplified

Cerebral small-vessel disease (CSVD) represents a major etiology of vascular cognitive impairment (VCI), driven by pathological processes such as cellular senescence and neuroinflammation. Among these, microglia-the brain's specialized immune cells-play a key role in driving neuroinflammation through their senescence, thereby exacerbating cognitive dysfunction. Although signal transducer and activator of transcription 6 (STAT6) activation has been implicated in alleviating neuroinflammation and cognitive deficits in CSVD, the underlying mechanisms remain unclear. This study sought to elucidate the roles of STAT6 and autophagy in the process of microglial senescence induced by CSVD. Using stroke-prone renovascular hypertensive rats (RHRSP) and chronic hypoxia-treated BV2 cells to assess cognitive function, microglial senescence, and autophagy, we observed that phosphorylation-mediated STAT6 activation significantly suppressed microglial senescence. Mechanistically, we found that phosphorylated STAT6 (pSTAT6) enhanced autophagy, which reduced the burden of senescent microglia and thereby ameliorated CSVD-induced VCI. These findings provide insights into the potential of targeting the STAT6 pathway in VCI associated with CSVD.

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PubMed

STAT6 Controls Cell Cleanup to Affect Brain Immune Cell Aging in Thinking Problems from Small Blood Vessel Disease

Abstract

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