The sense that one is living a meaningful life is associated with positive health outcomes, but less is known about the role of changes in sense of meaning. This outcome-wide analysis investigated bidirectional associations between changes in ratings of doing worthwhile things in life and 32 factors in 6 domains of human function in 5,694 men and women (M = 66.65 years) from the English Longitudinal Study of Ageing. Participants rated the extent they felt that the things they did in life were worthwhile in 2012 and 2014. Analyses were adjusted for age, gender, education and social class, and were weighted for non-response. We found that health (e.g. few chronic diseases, no chronic pain), emotional wellbeing (e.g. few depressive symptoms, good sleep), greater physical activity, social factors (e.g. close relationships, friends, organizational membership, volunteering, cultural engagement), and economic factors (wealth, income), at baseline were associated with 2 year increases in worthwhile ratings. Conversely, increases in worthwhile ratings over 2 years were related to more favourable health, emotional, behavioural, and social changes between 2012 and 2016 independently of baseline levels. These bidirectional relationships highlight the importance of maintaining worthwhile activities at older ages.