ADCY8 and heart failure: However, other studies have shown cardiac overexpression of AC8 to cause early and accelerated cardiac remodeling, resulting in development of heart failure and a shortened life span, suggesting that alterations in cAMP/PKA signaling can hasten cardiac aging, in part via the glycogen-synthase-kinase 3α/β (GSK3α/β) phosphorylation pathway (Mougenot et al., 2019).