The circulating milieu of bottlenose dolphins (Tursiops truncatus) may hold the key to preventing arterial aging

Abstract

Enhanced arterial function (high endothelial function and low aortic stiffness) is essential for the dive response and survival of cetaceans, given the demand to dive for feeding throughout their long lifespan. In humans, endothelial function is reduced with diving and aging, and large arteries stiffen with advanced age. Since reduced arterial health can limit health lifespan and cetaceans are long-lived, cetaceans may have preserved arterial health with advancing age. We tested if the circulating milieu (bioactive molecules in the serum) of young (n=16) and mid-life/older (ML/O; n=4) adult bottlenose dolphins would transfer the same arterial aging phenotypes as the serum of age-equivalent humans using an innovative technique. Excised arteries from young (5 mo) and old (25 mo) wildtype C57BL/6N mice were incubated ex vivo with 5% sex-matched adult human or bottlenose dolphin serum. Endothelial function was assessed as carotid artery endothelium-dependent dilation (EDD) to increasing doses of acetylcholine, and aortic stiffness as elastic modulus, a measure of intrinsic mechanical wall stiffness. Differences were assessed via 2-way ANOVAs; post hoc analyses were conducted between age groups within species. Peak EDD and aortic stiffness worsened in young mouse arteries following exposure to ML/O adult human serum (P<0.001 and P=0.001). These measures improved in old mouse arteries after exposure to young adult serum (P=0.001 and P=0.044). In contrast, old mouse arteries with old dolphin serum behaved like young mouse arteries with young dolphin serum for both, peak EDD (young v. ML/O serum donor in young arteries, P=0.773; in old mouse arteries, P=0.942) and aortic stiffness (young v. ML/O serum donor in young aortic rings, P=0.974; in old aortic rings P=0.157). These results suggest that the circulating milieu of bottlenose dolphins may be geroprotective. More research is needed to confirm these observations, elucidate the underlying mechanisms, and explore its potential applications for human medicine.