LOX is heightened in normal and tumor breast tissue in obese patients by activation of hypoxia-inducible factor 1a (HIF-1a) which interacts with the hypoxia response element located in the LOX promoter region, suggesting that combined obesity and aging promote crosslinking [118, 119] In addition, the aged ECM is associated with higher levels of proinflammatory cytokine release, which encourages cancer cell invasiveness and cell migration [115]. Here, LOX is linked to obesity due to melanocortin 4 receptor deficiency.