Effect of a caloric restriction regimen on the angiogenic capacity of aorta and on the expression of endothelin-1 during ageing.

Ageing is accompanied by impaired angiogenesis, as well as by a deficient expression of several angiogenic growth factors and the alteration of endothelial functions. Caloric restriction (CR) is the only intervention that can extend lifespan and retard age-related-decline functions in mammals by reducing the rate of ageing and the progression of the associated diseases. Herein, we have investigated the effects of ageing and of a caloric restriction regimen (mild or severe) on the angiogenic response and on the expression of endothelin-1 (ET-1) in the aorta of male 3-, 12- or 24-month-old Sprague-Dawley rats fed ad libitum (AL), fed ad libitum and fasted 1 day a week (mild CR) or fasted every other in alternate days (severe CR). Our findings, using the rat aorta ring assay, show that the angiogenic capacity of aorta decreases with ageing in the oldest rats only. Furthermore, caloric restriction counteracts the age-related changes caloric restrictions actually give raise to a similar recovery. Interestingly, the mRNA ET-1 levels as well as ET-1 expression in aorta sprouting decreases both in middle and in aged animals. Mild and severe caloric restriction regimens prevents ET-1 changes.