Aging alters vascular mechanotransduction: Pressure-induced regulation of p70S6k in the rat aorta

Physical forces are important regulators of vascular structure and function though it is unknown how aging may affect the ability of the vasculature to respond to mechanical stimuli. We investigated the pressure-induced activation of ribosomal S6-kinase (p70S6k) and its pathway-related proteins (Akt, GSK-3 beta, SHP-2, PTEN) in aortae from young adult (6 month), aged (30 month), and very aged (36 month) Fischer 344 x Brown Norway F1 hybrid rats. With aging, the aortic tissue content of Akt. SHP-2, and PTEN was significantly increased while total p70S6k and GSK-3p were unchanged. By comparison, the basal phosphorylation of p70S6k at Thr 389 and Thr 421/Ser 424 was increased (similar to 40%) and unchanged, respectively, while Akt decreased (-37%), GSK-3p was unchanged, SHP-2 increased (similar to 73.5%), and PTEN increased (similar to 120%) in the aortae of very aged rats. Acute pressurization of aortae resulted in similar increases in phosphorylation of Akt among the different age groups. By comparison, pressure-induced phosphorylation of p70S6k at Thr 389, GSK-3p and SHP-2 decreased; whereas, PTEN dephosphorylation was increased in 36-month versus 6-month aortae. The results indicate marked alterations in the p70S6k signaling pathway with aging. The implications of these findings on age-associated vessel remodeling are discussed. (c) 2005 Elsevier Ireland Ltd. All rights reserved.