Age-Related Impairment of Angiogenesis Impacts Proficient Regeneration in Zebrafish

Zebrafish are one of the few vertebrate species capable of repeatedly regenerating major tissue loss without scarring. This ability is impacted by aging, however, as noted here. Researchers find that the age-related loss of angiogenesis capacity impairs regeneration. It is known that capillary density declines with age, hand in hand with impaired angiogenesis, and it is hypothesized that the consequent reduced delivery of oxygen and nutrients is an important contribution to many aspects of aging.

Impaired wound healing is associated with aging and has significant effects on human health on an individual level, but also the whole health care sector. Deficient angiogenesis appears to be involved in the process, but the underlying biology is still poorly understood. This is at least partially being explained by complexity and costs in using mammalian aging models.

To understand aging-related vascular biology of impaired wound healing, we have utilized zebrafish and turquoise killifish fin regeneration models. The regeneration of caudal fin after resection was significantly reduced in old individuals in both species. Age-related changes in angiogenesis, vascular density, and expression levels of angiogenesis biomarker VEGF-A were observed. Furthermore, an anti-angiogenic drug, vascular endothelial growth factor receptor blocking inhibitor SU5416, reduced regeneration indicating a key role for angiogenesis in the regeneration of aging caudal fin despite aging-related changes in vasculature.

Taken together, our data indicates that these fish fin regeneration models are suitable for studying aging-related decline in wound healing and associated alterations in aging vasculature.


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