Life-span theories explain successful aging with an adaptive management of emotional experiences like regret. As opportunities to undo regrettable situations decline with age, a reduced engagement into these situations represents a potentially protective strategy to maintain well-being in older age. Yet, little is known about the underlying neurobiological mechanisms supporting this claim. We used a multimodal psychophysiological approach in combination with a sequential risk-taking task that induces the feeling of regret and investigated young as well as emotionally successfully and unsuccessfully (i.e., late-life depressed) aged participants. Responsiveness to regret was specifically reduced in successful aging paralleled by autonomic and frontostriatal characteristics indicating adaptive shifts in emotion regulation. Our results suggest that disengagement from regret reflects a critical resilience factor for emotional health in older age.