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Aging stiffens the tissues that surround our cells. New research shows this biomechanical stress can rewire metabolism, fueling cancerous growth in the prostate.
The Discovery:
Scientists found that basement membrane stiffness, caused by age-related collagen crosslinking, activates the receptor Endo180 in prostate epithelia. This switch forces cells to ramp up mitochondrial oxidative phosphorylation (OXPHOS), driving hallmark cancer behaviors long before genetic mutations appear.
The Science:
Collagen crosslinking from AGEs stiffens prostate basement membranes with age.
Endo180 detects stiffness and disrupts its suppressor complex with CD147, enabling epithelial-to-mesenchymal transition.
This reprogramming boosts OXPHOS genes, mitochondrial mass, and oxygen consumption.
Cancer hallmarks emerge: resistance to cell death, unchecked proliferation, inflammation, invasion, and metastasis.
In low-grade Gleason 6 tumors, Endo180 couples with OXPHOS and CD147, but this uncouples in higher-grade cancers, marking a potential biomarker for progression.
Endo180 expression rises with biological age, linking tissue aging directly to tumor initiation.
Your Action:
This research is early but emphasizes how lifestyle factors that accelerate AGEs (advanced glycation end-products), like chronic high sugar intake, may stiffen tissues and raise cancer risk.
Limit processed sugars, maintain metabolic health, and support collagen integrity through balanced nutrition and physical activity.
Bottom Line:
Age-driven tissue stiffening can switch on cancer metabolism, pointing to Endo180 as both a risk marker and therapeutic target.
Source:
Endo180 and basement membrane stiffness induce OXPHOS and neoplastic transformation in aging prostate epithelia. npj Aging. Rodríguez-Teja M, Pastro L, et al.
https://doi.org/10.1038/s41514-025-00259-4
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Disclaimer:
This newsletter is for informational purposes only and does not substitute professional medical advice. Always consult with a healthcare provider before making any changes to your health regimen.