Regenerative hallmarks of aging: Insights through the lens ofPleurodeles waltl

Abstract

AbstractBackgroundAging and regeneration are heavily linked processes. While it is generally accepted that regenerative capacity declines with age, some vertebrates, such as newts, can bypass the deleterious effects of aging and successfully regenerate a lens throughout their lifetime.ResultsHere, we used Optical Coherence Tomography (OCT) to monitor the lens regeneration process of larvae, juvenile, and adult newts. While all three life stages were able to regenerate a lens through transdifferentiation of the dorsal iris pigment epithelial cells (iPECs), an age-related decline in the kinetics of the regeneration process was observed. Consistent with these findings, iPECs from older animals exhibited a delay in cell cycle re-entry. Furthermore, it was observed that clearance of the extracellular matrix (ECM) was delayed in older organisms.ConclusionsCollectively, our results suggest that although lens regeneration capacity does not decline throughout the lifespan of newts, the intrinsic and extrinsic cellular changes caused by aging alter the kinetics of this process. By understanding how aging affects lens regeneration in newts, we can gain important insights for restoring the age-related regeneration decline observed in most vertebrates.