Agarononaose from red algae delays cardiomyocyte aging by improving mitochondrial function via enhanced oxidative phosphorylation: A mitochondrial transplantation perspective

This study found that agarononaose (A9) exhibits the most significant anti-senescence effect on HL-1 cardiomyocytes among agarose-derived oligosaccharides. Meanwhile, we found that this feature appears to be associated with the mechanism of nutritional intervention dysregulation. Further investigation revealed that A9 improved a series of mitochondrial mechanisms, including oxidative phosphorylation (OXPHOS), mitochondrial membrane potential, oxidative stress, the mitochondrial unfolded protein response (UPR mt ), mitochondrial biogenesis, and mitochondrial dynamics. Importantly, through mitochondrial transplantation experiments and OXPHOS inhibition, it was demonstrated that the enhancement of OXPHOS is a primary mechanism through which A9 ameliorates cellular senescence. Moreover, this bioactivity could be transferred to recipient cells via mitochondrial transplantation. This study identifies a natural marine oligosaccharide as a potential functional food and pharmaceutical agent for ameliorating cardiac cell senescence, and elucidates its key mechanisms. Furthermore, we propose a novel research approach based on mitochondrial transplantation for investigating drug interventions targeting mitochondrial function. • A9 exhibits the strongest activity in delaying the senescence of cardiomyocytes. • A9 localizes to mitochondria after entering cells. • A9 extensively improved mitochondrial function. • A9 may exert its biological effects by enhancing oxidative phosphorylation.