Structural and metabolic signatures of cardiac aging in African turquoise killifish (Nothobranchius furzeri).

Aging induces profound structural remodeling of the heart, yet experimental investigation of cardiac aging remains limited due to the long lifespan of most vertebrate models. The African turquoise killifish (Nothobranchius furzeri) provides a unique opportunity to analyze age-related cardiac changes within an experimentally accessible timeframe. While previous studies have primarily focused on the short-lived GRZ strain, cardiac aging in long-lived strains remains poorly characterized. In this study, we examined cardiac aging in the long-lived MZCS strain of N. furzeri using histological analyses combined with quantitative image analysis. Age-related changes in cardiac morphology, myocardial structure, extracellular matrix remodeling, accumulation of PAS-positive (glycogen-like) material, and senescence-associated β-galactosidase (SA-β-Gal) activity were evaluated by comparing young (1.5 months) and old (7-10 months) fish of both sexes. Old fish exhibited ventricular enlargement, epicardial thickening, valvular abnormalities, and prominent interstitial myocardial fibrosis. In contrast to mammals and zebrafish, cardiomyocyte hypertrophy was not observed; instead, myocardial density was reduced, with marked thinning of peripheral trabeculae, indicating a species-specific mode of cardiac remodeling. Accumulation of glycogen-like material tended to be more pronounced in young fish, whereas the expression of most glucose metabolism-related genes showed no marked age-dependent changes. Notably, SA-β-Gal activity was robustly detected from early life onward, suggesting that elevated SA-β-Gal activity represents an intrinsic characteristic of the killifish heart rather than a simple marker of chronological aging. Together, these findings establish the long-lived MZCS strain of N. furzeri as a valuable histological model for investigating conserved and species-specific features of cardiac aging.