Figure 5. Histological and molecular signs of premature aging in the back skin of transgenic mice. (A-H) Representative histological images showing the back skin of 20-month-old Control mice (A) and the severe aging phenotype of the back skin of 20-month-old transgenic mice (B-D). (B-D) Note severe epidermal atrophy (compare insets in A with those of B and C; double-headed red arrow in D); foci of papillomatous hyperplasia (red arrows in C and D); numerous hyperplastic sebaceous glands, most of them orphan and grouped in the dermis (D); reduced number of HFs, and scarce or even lack of adipose tissue (compare A with B-D) in the back skin of the K5-CYLDC/S mice. (E-H) Tail skin of Control (E) and transgenic (F-H) mice. Note the presence of hyperplastic sebaceous glands and extensive epidermal atrophy (compare inset in E with those in F and G) in the tail of the K5-CYLDC/S mice. (I, J) WB of total protein extracts from skin of 12-month-old (I) and 6-month-old (J) showing elevated levels of p16, p19 and γH2AX in the K5-CYLDC/S mice. Tubulin and Actin are used as control loading. (K) WB of total protein extracts from the skin of Control mice from 1 to 33 months of age showing the decreased expression of CYLD as mice age. GAPDH is used as a control loading. White arrows: sebaceous glands; red arrows: papillomatous hyperplasia; double-headed red arrows: areas of epidermal atrophy. Scale bars: 250 μm (A-D); 200 μm (E-H).