Morphological analysis of skin in senescence-accelerated mouse P10

Senescence-accelerated mice (SAM) were established as a kind of group of related inbred strains that have been used as animal models for accelerated senescence and age-associated disorders. To analyze the characteristics of skin in SAM, the present study examined its morphology at the histological and ultrastructural levels. Histologic comparison of skin from senescence-accelerated-prone (SAM P10) and -resistant (SAM R1) mice revealed that the most characteristic features of SAM P10 were remarkable increases in the number of mast cells and in the density of collagen fibers in the dermis. Therefore, cutaneous allergic responsiveness and the proliferative activity of fibroblasts were also examined. Ultrastructurally, mast cells in the skin of SAM P10 possessed specific granules which exhibited considerable heterogeneity in electron density and various degrees of degranulation. In contrast, mast cells in the skin of control SAM R1 possessed a population of stable granules. Mast cell granules were frequently in contact with fibroblasts and were in close apposition to collagen fibers in the dermis of SAM P10. The collagen bundles were disorganized, and various diameters of collagen fibers were observed. SAM P10 demonstrated a significantly reduced wheal-and-flare reaction to histamine and tachykinins such as substance P, which suggests that skin aging may cause reduced sensitivity of mast cells and/or blood vessels to extrinsic stimuli. An in-vitro study using organ and monolayer culture demonstrated that the proliferative capacity of fibroblasts in the skin of SAM P10 was reduced in comparison with SAM R1. This is the first report that demonstrates the detailed morphological characteristics of skin in SAM P10. The findings obtained suggest that SAM P10 is a useful animal model of aged human skin, because of its many similar morphological features, including the reduction of the cutaneous allergic response, represented by neurogenic inflammation via the axon reflex, and its decreased fibroblast proliferation.