Figure 4. Histopathological signs of premature aging in the back skin of young (5- and 8-month-old) transgenic mice. Representative histology of the back skin of 5-month-old Control and transgenic mice (A-G). (A) Histology of the back skin of a Control mouse. Observe the presence of small sebaceous glands (white arrow) and 3 layers of keratinocytes in the interfollicular epidermis (higher magnification is showed in the inset). (B-E) The epidermis of the K5-CYLDC/S mice shows frequent and extensive areas of atrophy (double-headed red arrows in B and C; also compare the inset in B with that of A); as well as papillomatous hyperplasia (red arrow in C) and epidermal ridges (black arrows in E and G). Abundant hyperplastic sebaceous glands -often orphan, were detected (white arrows in C-E). (F-G) Observe the scarce adipose tissue present in the skin of the transgenic mice (compare the length of the double-headed black arrows). Representative histology of the back skin of Control (H) and transgenic mice (I, J) of 8-month-old. Observe in the K5-CYLDC/S mice the presence of papillomatous hyperplasia (red arrows in I); epidermal ridges (black arrows in J); abundant hyperplastic sebaceous glands (white arrows), some of them orphan (without HF) (I), and patchy epidermal atrophy associated to moderate hyperkeratosis (compare the inset in H with those of I and J). Representative histological images of the tail skin of Control (K) and transgenic mice (L-N). Note in the skin of transgenic mice the presence of hyperplastic sebaceous glands, most of them orphan (white arrows), and epidermal atrophy (compare the insets in K with those of M and N). Images of the histology of both K5-CYLDC/S-X and K5-CYLDC/S-A are shown. White arrows, sebaceous glands; black arrows: epidermal ridges; double-headed red arrows: areas of epidermal atrophy. Scale bars: 150 μm (C, E); 180 μm (A, B, D, I, J, L-N); 200 μm (H, K) and (F, G) 350 μm.