Proposed model for MMP induction in photoaging

In the epidermis, first, UVB-generated aromatic ligands activate AhR, which suppresses NER activity. Second, enhanced DNA damage is detected by ATM kinase, which subsequently activates p38 and JNK MAPK pathways. Third, phosphorylated SP1 binds the GC-rich promoter regions of MMP2 and MMP11 (possibly alongside MMP9) to promote their transcription.

At the same time, in both the dermis and epidermis, UVA-generated ROS ultimately leads to the activation of AP-1, leading to the upregulation of MMP1, MMP3, and MMP9. Both sets of MMP genes could then contribute to the signs of photoaging in skin with MMP-2, primarily degrading type IV collagen in the basement membrane, and other MMPs degrading types I/III collagen in the dermis. By antagonizing AhR and promoting clearance of UVB-generated DNA damage, B12 and folic acid could potentially counteract photoaging.