The Lymphatic Biology of Aging

It is only recently that scientists and clinicians have begun to awaken to the concept that, among adult humans, there is a non-homogeneous expression of the altered function that characterizes both “normal” and “diseased” individuals. Most prominently, this transition has given rise to the phenomenon of gender studies in a variety of disease states and in manifestations related to human health.^1–5 In our discipline of lymphatic biology and medicine, we have long been aware of gender influences upon the expression of both primary and secondary lymphedema. ⁶

Similarly, there is now a small but growing awareness of the biology of aging in health and disease. Without question, the biology of aging represents the raison d'être for the National Institute on Aging, which supports prospective investigation of these phenomena in a variety of disease settings.

To date, there has been little awareness of the role of aging in the function of the lymphatic circulation. However, in the current issue, Thangaswamy et al. have directed their attention to a specific manifestation of this phenomenology. ⁷ Previously, it has been recognized that aging is associated with a decline in the contractility of the mesenteric vessels in rats, ⁸ although the contributory mechanisms were largely not elucidated. With the current investigation, they found that in the mesenteric lymphatic vessels of aged rodent subjects, there was evidence of increased levels of cellular superoxide and mitochondrial reactive oxygen species, thus delineating the presence of both an increase in oxidative stress and a decrease in antioxidant activity. The implication of these findings is that oxygen-derived radicals may contribute to the previously observed, age-dependent decline in lymphatic pump function. Clearly, if these mechanisms can be extrapolated to other species and to both visceral and non-visceral lymphatic vasculature, it will have distinct future implications for our understanding of aging-related disease expression and to the application of effective therapeutics.