Genes & diseasesOct 20, 2026

Glis1 supports cell metabolism by increasing H3K18 lactylation to reduce nerve cell aging after spinal cord injury

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 21, 2026

Abstract

A post-spinal cord injury rise in neuronal lactate levels is associated with increased cellular senescence.

Glis1 may play a critical role in reprogramming senescent cells and enhancing genomic stability through lactylation.
Histone lactylation, an epigenetic modification, becomes more prominent after spinal cord injury due to elevated lactate levels.
Upregulation of Glis1 appears to reduce neuronal senescence and promote histone lactylation.
The downstream target secretogranin II (SCG2) may negatively impact glycolytic metabolism and lactylation, thus suppressing neuronal senescence.
A novel regulatory mechanism involving Glis1, histone lactylation, and SCG2 is suggested to influence neuronal senescence following spinal cord injury.

Simplified

Neuronal senescence is a significant factor impeding spinal cord injury (SCI) repair. Research indicates that Glis1, a Kruppel-like zinc finger transcription factor, is pivotal in reprogramming senescent cells and enhancing genomic stability via lactylation. Histone lactylation, an epigenetic modification using lactate as a substrate, becomes prominent post-SCI due to increased neuronal lactate levels. However, the mechanisms linking neuronal senescence and histone lactylation following SCI remain poorly understood. This study elucidates the roles of Glis1, H3K18 lactylation, and neuronal senescence through comprehensive in vivo and in vitro investigations. The findings reveal a post-SCI rise in neuronal lactate levels, accompanied by cellular senescence. Furthermore, upregulation of Glis1 attenuates senescence and promotes histone lactylation. The downstream target secretogranin II (SCG2), identified via ChIP-seq and RNA-seq, was found to exert negative feedback on glycolytic metabolism and lactylation, thereby suppressing neuronal senescence. These results unveil a novel regulatory mechanism of Glis1 in neuronal senescence following SCI through the p300/H3K18la/SCG2 axis, offering a new therapeutic target for spinal cord repair.

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Glis1 supports cell metabolism by increasing H3K18 lactylation to reduce nerve cell aging after spinal cord injury

Abstract

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