The dermal-epidermal junction of human skin exhibits age-related remodelling, resulting in a flattened appearance and reduced surface area. Despite this, a paucity of information is available regarding which protein components change with advancing age. Here we report a significant reduction in the protein distribution of collagen IV (P<0.0001), collagen VII (P<0.001), collagen XVII (P<0.01), integrin β4 (P<0.001) and laminin-332 (P<0.0001) in intrinsically aged skin. The functional implication of this altered protein composition appears to be loss of structural integrity and may, in part, explain the increased fragility of aged skin.