Aging and survival of cutaneous microvasculature.

The growth and turnover of blood vessels in the skin is fundamental in normal development, wound repair, hair follicle cycling, tumor cell metastasis, and in many different states of cutaneous pathology. Whereas many investigations are focused on mechanisms of angiogenesis in the skin, the influence of cellular aging and replicative senescence (i.e., the inability, after a critical number of population doublings, to replicate) on microvascular remodeling events has received relatively less attention. In this article, we review the clinical and pathologic relationships associated with cutaneous vascular aging and update current knowledge of endothelial cell survival characteristics. A hypothesis is presented in which endothelial cell aging and survival are linked to molecular mechanisms controlling cell proliferation, quiescence, apoptosis, and cellular senescence. We review recent results demonstrating how activation of telomerase in human dermal microvascular endothelial cells affects their durability both in vitro and in vivo and conclude by linking these studies with current concepts involving endothelial cell precursors, control of postnatal somatic cell telomerase activity, and murine model systems.