Autophagy‐enhancing treatment reverses age‐associated large elastic artery stiffening and modulates arterial superoxide production, inflammation and collagen I

Abstract

Aging leads to stiffening of large elastic arteries associated with increased superoxide (O2‐) production, inflammation and collagen protein. Impairments in autophagy, a process that recycles damaged cellular components and influences oxidative stress and inflammation, may contribute to age‐related arterial stiffening. We tested the hypothesis that treatment with the natural disaccharide trehalose, an autophagy inducer, would reduce aortic pulse wave velocity (aPWV), a clinically important measure of arterial stiffness, and decrease superoxide production, inflammation and collagen I in old (O) male C57/BL6 mice. Autophagy was impaired in aorta from O (28 mo, n=6) vs. young (Y: 5 mo, n=6) mice as indicated by a ~40% reduction (p<0.05) in beclin‐1 and LAMP‐2a, and these markers were restored by trehalose treatment (4 weeks, 20 g/L drinking water) in O mice. aPWV was higher in O vs. Y mice (471 ± 23 vs. 405 ± 25 cm/s, p<0.05), and trehalose reduced aPWV in O mice (pre: 478 ± 32 vs. post: 417 ± 18 cm/s, p<0.05). Trehalose treatment reversed age‐associated increases in aortic O2‐ production and inflammatory cytokines (tumor necrosis factor α and interleukin‐1), and reduced aortic collagen I by ~50%. Our results suggest that autophagy may be a promising therapeutic target for treating age‐associated large elastic artery stiffening, possibly by reducing O2‐/inflammation modulation of collagen.