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Description: Although hobbies can improve quality of life (QoL), the role that music might play in healthy aging still needs to be established. The aim of the present study was to investigate the causal influence of piano practice on QoL in seniors. Furthermore, we aimed to identify brain regions of the reward circuit that are related to QoL and piano practice. The present randomized controlled trial included 156 older, healthy participants. All participants were randomly assigned to either piano practice or music listening groups and attended weekly 60-min lessons for 12 months. At 0, 6, 12, 18, and ∼48 months, QoL was assessed using the WHOQOL-BREF questionnaire. Gray matter volume was evaluated from T1-weighted MRI data acquired at the first four time points. Practicing piano positively impacted the psychological (log-odds 0.13, 90% credible interval [0.01, 0.26]), physical (0.22 [0.05, 0.39]), and environmental (0.18 [0.01, 0.35]) QoL. Social QoL did not change between groups. Furthermore, changes in QoL were positively associated with bilateral amygdala and left pallidal volume increases. In conclusion, offering piano lessons could be a worthwhile approach to promote healthy aging and improve seniors’ QoL.

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