Aging Activates the Immune System and Alters the Regenerative Capacity in the Zebrafish Heart

Age-associated organ failure and degenerative diseases have a major impact on human health. Cardiovascular dysfunction has an increasing prevalence with age and is one of the leading causes of death. In contrast to humans, zebrafish have extraordinary regeneration capacities of complex organs including the heart. In addition, zebrafish has recently become a model organism in research on aging. Here, we have compared the ventricular transcriptome as well as the regenerative capacity after cryoinjury of old and young zebrafish hearts. We identified the immune system as activated in old ventricles and found muscle organization to deteriorate upon aging. Our data show an accumulation of immune cells, mostly macrophages, in the old zebrafish ventricle. Those immune cells not only increased in numbers but also showed morphological and behavioral changes with age. Our data further suggest that the regenerative response to cardiac injury is generally impaired and much more variable in old fish. Collagen in the wound area was already significantly enriched in old fish at 7 days post injury. Taken together, these data indicate an ‘inflammaging’-like process in the zebrafish heart and suggest a change in regenerative response in the old.