FIG. 6.
Autophagy in kidney homeostasis and aging. (A) Autophagy maintains podocyte homeostasis. Autophagy deficiency is compensated by elevated proteasome activity in podocytes with Atg5 gene deletion in adult mice (ages 8–12 months of age), resulting in mild proteinuria. In aged Atg5Δpodocyte mice (20–24 months of age) compensatory proteasome activitydecreases, leading to severe proteinuria, loss of podocytes, and glomerulosclerosis. (B) Autophagy maintains tubular homeostasis. Double knockout of Atg5 in PTC and DTC results in kidney dysfunction. (C) Autophagy protects against aging-associated CKD. Activation of autophagy by calorie restriction protects aging kidney from hypoxia-induced oxidative stress and mitochondrial damage, and attenuates aging-associated kidney dysfunction. CKD, chronic kidney diseases; DTC, distal tubular cells. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars