Blood flow and angiogenesis: Major mechanisms mediating healthful longevity

While human lifespan has increased dramatically over the past century, the extension of healthspan, the period free of chronic age-related disease, has lagged behind. Blood flow and angiogenesis are significantly reduced in aging humans, playing a crucial role in mediating cardiovascular disease and heart failure - major causes of reduced lifespan. However, these mechanisms have not been studied as extensively as cellular and molecular mechanisms in animal models. Healthful aging, due to angiogenesis and improved blood flow, is the focus of this review. Here we considered 25 rodent models of healthful longevity. Seven of these had direct evidence of improved blood flow and angiogenesis contributing to enhanced exercise, preserved organ function and resistance to ischemic injury and heart failure. Four others exhibited mixed results, but did not show clearly improved blood flow and angiogenesis Fourteen models did not examine these mechanisms. The mechanisms mediating the improved angiogenesis and, as a result enhanced blood flow, include not only vascular growth hormones and mitochondrial protection, but also a role for a less well studied factor, namely brown adipose tissue (BAT). For example, a recently studied rodent model, the Regulator of G Protein Signaling 14 knockout mouse, exhibited a marked increase in angiogenesis and improved blood flow through a BAT mechanism, i.e., when BAT was removed, blood flow and angiogenesis were no longer improved, but when it was transplanted into wild type mice, blood flow and angiogenesis were enhanced. Given the potential importance of angiogenesis and improved blood flow, these factors need to be considered for future healthful longevity therapeutic translation.