Mechanisms of Ageing and Development · Dec 1, 2022

Pathological implication of CaMKII in NF-κB pathway and SASP during cardiomyocytes senescence

By Li T, Meng Y, Ding P et al.

Senescence-associated secretory phenotype (SASP) could be developed during heart ageing. But the role of SASP in cardiomyocytes senescence and its molecular mechanism remains undetermined. In this study, we observed elevated Ca²⁺/calmodulin -dependent protein kinase II (CaMKII) activation in both physiological aged heart and premature senescent cardiomyocytes. Notably, we confirmed the gradual SASP development induced by NF-κB activation in long-term cultured cardiomyocytes. Transgenic inhibition of CaMKII in mice (AC3-I mice) alleviated the NF-κB activation, chronic sterile inflammation and ageing-associated cardiomyopathy. Correspondingly, pharmacological inhibition of CaMKII with KN93 mitigated SASP and hindered cardiomyocytes senescence. Meanwhile, increased NF-κB activation and exacerbated cardiomyocytes senescence were observed with transgenic CaMKII activation. Collectively, our results indicated that the increased CaMKII activation accompanying ageing could aggravate NF-κB activation and SASP development and facilitate cardiomyocytes senescence and heart ageing.

doi.org/10.1016/j.mad.2022.111758Open accessPubMed 36462537Mechanisms