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More help Essentiality of the Key Events The essentiality of KEs can only be assessed relative to the impact of manipulation of a given KE (e.g., experimentally blocking or exacerbating the event) on the downstream sequence of KEs defined for the AOP

After M1 polarization, macrophages release large amounts of Fe 2+ via ferritin autophagy mediated by nuclear receptor coactivator 4 (NCOA4), which not only promotes ferroptosis but also causes the further release of ferroptosis-promoting factors into the cornea, RPE, and RGCs, forming a vicious cycle in the ocular microenvironment

This natural decrease is a major reason why skin texture changes, color shifts, and wrinkles begin to form as we age

From contributor D: I think Contributor P has hit this one dead on

Reference Cummins, OHagan, Jablonkai, Cole, Hehn, Werck-Reichhart and Edwards2003