Fishing for Keys to Longevity in the Heart of the Greenland Shark

The Greenland shark (Somniosus microcephalus) is the longest living vertebrate on the planet with a life span of at least 272 years. This extreme longevity is particularly interesting for cardiac studies, because age is synonymous with heart disease in humans. Mitochondria are dynamic subcellular organelles whose individual shape, organisation, and function are known to change with age. Similarly, age can alter nuclear form and function particularly in diseases associate with premature aging. We have used electron microscopy imaging and machine learning approaches, combined with metallomics and biochemical analyses in cardiac tissue from Greenland sharks between ~20 and ~200 years to better understand the role of these two key organelles in extreme longevity. We show mitochondrial volume densities were similar among individuals regardless of age (~20% of the myocardial volume). However, greater inner mitochondrial membrane (IMM) content was observed in larger (and thus presumably older) sharks. Metallomics showed that copper-levels were low in Greenland sharks compared with other species and did not change with age, which may indicate that the copper-based Complex IV of the mitochondrial respiratory-chain is less abundant in this species. Biochemical analyses revealed that little impact of age on mitochondrial function. Finally, we observed no change in nuclear morphology or heterochromatin content across the life span of the Greenland sharks assessed in this study. However, all sharks retained comparatively small nucleoli which is a hallmark of longevity across metazoans