fig7

Figure 7. Loss of proteostasis in aging and AF. An impairment of proteostasis during aging underlies dysregulation of autophagy and the ubiquitination-proteasome system (UPS), leading to the accumulation of misfolded protein aggregates. These aggregates can be managed by restoring the function of molecular chaperones such as heat shock protein (HSP) by geranylgeranylacetone (GGA). Whether this restoration of HSP in the aging heart could prevent AF remains uncertain (indicated by a question mark). Notably, AF may be associated with excessive autophagy activation due to ER stress, which can be inhibited by 4-Phenylbutyric acid (4-PBA) treatment. The unresolved aggregates induce cellular stress, contributing to inflammation and fibrosis in the heart, eventually creating an arrhythmogenic substrate that allows for the occurrence and perpetuation of AF. Dashed lines indicate disruptions in normal physiological processes, leading to age-related consequences. The figure was generated with BioRender.com.