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

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 <i>(Nothobranchius furzeri)</i> 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 <i>N. furzeri</i> 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(definition)-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 <i>N. furzeri</i> as a valuable histological model for investigating conserved and species-specific features of cardiac aging.