Fig. 6.
Pak2 depletion delays the onset of aging phenotypes and increases life span in a mouse model of accelerated aging. (A) Overall survival curves for Pak2+/+;BubR1H/H (n = 28) and Pak2H/H;BubR1H/H (n = 27) mice. The median overall survival of combined Pak2H/H;BubR1H/H mice is 159 d, about a 30% extension in life span compared with Pak2+/+;BubR1H/H mice. (**P < 0.01.) (B and C) Incidence of cataract formation in Pak2+/+;BubR1H/H (n = 18) and Pak2H/H;BubR1H/H (n = 16) mice. (*P < 0.05.) (D and F) Cross section of a cataractous lens from 4-mo-old Pak2+/+;BubR1H/H and Pak2H/H;BubR1H/H mice stained with hematoxylin and eosin (H&E). Hematoxylin stain, showing blues in bottom images, indicates posteriorly located epithelial cells (mean ± SEM, **P < 0.01, n = 4 independent biological replicates). (E and G) Cross section of IAT from 4-mo-old Pak2+/+;BubR1H/H and Pak2H/H;BubR1H/H mice stained with H&E. Cross-sectional area was obtained using ImageJ software (mean ± SEM, n = 4 independent biological replicates). (**P < 0.01.) (H and I) Western blots of eye and IAT extracts from 4-mo-old Pak2+/+;BubR1H/H, Pak2H/H;BubR1H/H, and wild-type mice probed with Pak2 and p16INK4a antibody. α-Tubulin served as loading control. MEF lysates were used as an antibody-specific band control.