Lactate accumulating in degenerated intervertebral discs drives histone H3K18 lactylation, which suppresses CD248 both by recruiting SMARCA5 to its promoter and by accelerating its ubiquitin–proteasome degradation. Loss of CD248 removes Hedgehog-pathway support for nucleus pulposus cells, increasing apoptosis and extracellular matrix breakdown. The work identifies a metabolite-to-chromatin pathway linking local energy metabolism to structural tissue failure in the spine.
Key Points
- Degenerated disc cells show elevated lactate and histone lactylation
- H3K18 lactylation suppresses CD248 transcriptionally and via proteasomal degradation
- CD248 loss drives nucleus pulposus apoptosis and matrix breakdown
Longevity Analysis
The intervertebral disc is avascular and glycolysis-dependent, so lactate clearance depends entirely on diffusion through endplates that stiffen with age — making accumulated metabolic byproduct an epigenetic signal rather than inert waste. Spinal degeneration here is not simply mechanical wear but a metabolic state writing itself into chromatin, with downstream consequences for the tissue's capacity to rebuild its own matrix. Preserving endplate perfusion, mitochondrial efficiency, and movement patterns that support nutrient exchange becomes a plausible lever on structural resilience, and lactylation markers may eventually serve as a readable signal of disc metabolic stress long before pain or imaging changes appear.
Original published by Wiley Aging Cell, by Yiming Ma, Tuo Shao, Qichang Gao, Jiaao Gu, Wenbo Zhan, Shuning Han, Song Li, Zhange Yu .