Resilience to cardiac aging in Greenland shark <i>Somniosus microcephalus</i>

Abstract The Greenland shark ( Somniosus microcephalus ), with a lifespan exceeding 400 years, represents a unique model for studying vertebrate longevity. Here, we characterize its cardiac aging profile and compare it with two other species: the deep-sea shark Etmopterus spinax and the short-lived teleost Nothobranchius furzeri . Histological analysis revealed extensive interstitial and perivascular fibrosis throughout the ventricular myocardium of S. microcephalus , affecting both compact and spongy layers of both sexes. This fibrotic pattern was absent in E. spinax and N. furzeri , suggesting it is a specific feature of S. microcephalus . We also observed extreme lipofuscin accumulation within cardiomyocytes of S. microcephalus , which correlates at the ultrastructural level with abundance of damaged mitochondria and the presence of strikingly enlarged lysosomes filled with electrondense material of likely mitochondrial origin. Additionally, in the myocardium of S. microcephalus we found abundant deposition of the oxidative stress marker 3-nitrotyrosine. Remarkably, despite showing multiple canonical markers of aging such as fibrosis, lipofuscin accumulation, and oxidative damage, S. microcephalus individuals appeared healthy and physiologically uncompromised at the time of capture. These findings suggest that S. microcephalus has evolved resilience to molecular and tissue-level aging hallmarks, supporting sustained cardiac function over centuries and offering new insights into the mechanisms of extreme vertebrate longevity.