Stress‐Mediated Hormetic Modulation of Aging, Wound Healing, and Angiogenesis in Human Cells

Abstract:  Aging is amenable to intervention and prevention by mild stress‐induced hormesis. Previously, we have reported that repeated mild heat stress has antiaging and other beneficial effects on growth and a range of cellular and biochemical characteristics of normal human skin fibroblasts and keratinocytes undergoing aging in vitro. We have also established a model system of sugar‐induced premature senescence in human cells, which can be useful for monitoring the protective and hormetic effects of other treatments. We have now initiated studies on testing the hormetic effects of glyoxal and heat shock on the wound‐healing capacity of skin fibroblasts and on the angiogenic ability of endothelial cells. The effects of glyoxal on the extent of wound closure in vitro showed a typical biphasic hormetic curve with 20‐40% stimulation at lower doses (up to 0.125 mmol) and more than 50% inhibition at concentrations above 0.5 mmol. In the case of angiogenesis by endothelial cells, measured by the standard tube formation assay on Matrigel, a prior exposure to mild heat shock at 41°C for 1 h increased the total tube length and total number of junctions by 30–60% and 10–14%, respectively. In contrast, a severe heat shock at 42.5°C had slightly inhibitory effects on total tube length and the number of junctions. These data add to the ever‐growing body of evidence in support of the view that mild stress‐induced hormesis can be a useful approach for the modulation, intervention, and prevention of aging and age‐related impairments.