• β1-AA disrupts cardiac autophagy rhythm by reducing PER2 protein expression, leading to decreased LC3 levels.
• PER2 knockdown exacerbates β1-AA-induced autophagy inhibition, while PER2 overexpression restores it, confirming PER2's protective role.
• mTORC1 activation mediates the effect of PER2 reduction on autophagy inhibition, as rapamycin reverses the effect.
• This study offers a circadian-rhythm-based therapeutic target for heart failure, highlighting PER2 and mTORC1 as potential intervention points.