Sex differences in human wound healing. (a) Collagen VII immunostaining at day 14 after wounding illustrates complete reformation of the basement membrane in the young female (YF, left, arrow), whereas staining in the elderly female (EF) is patchy and punctate (green arrow), and is significantly fainter in the elderly male (EM, green arrow). NS, normal skin adjacent to wound. Young males healed similarly to young females, thus only the young female section is shown. (b) Quantification of collagen VII immunostaining where 0 = normal (unwounded) skin intensity. A significant (*P < 0.05) decrease in staining was apparent at day 14 in the elderly males. (c) TNF-α immunostaining at day 7 increased markedly with age, and dramatically in the elderly male. YM, young male. Arrows indicate positively staining macrophages. (d) Systemic testosterone levels in elderly health status–defined human males strongly correlates with impaired healing of acute wounds (increased wound area at day 7; P = 0.001; r2 = 0.459).