Our previous work showed that pericytes can promote human skin regeneration independently of regulating angiogenesis1. We therefore sought to identify novel mechanisms by which they increase keratinocyte proliferation and regeneration. We performed microarray analysis on pericytes derived from neonatal versus adult human skin identifying consistent changes in gene expression with ageing. Gene ontology analysis revealed 25 genes consistently overexpressed by pericytes in young skin, involved in tissue remodelling and wound repair impacting on cell adhesion and extracellular matrix re-modelling. Notably two proteoglycans: versican (VCAN) and lumican (LUM) exhibited a decline in expression at mRNA level with increasing age. We subsequently demonstrated that both proteoglycans localized to the dermis of the skin and that their levels gradually diminished quantitatively with increasing age. Adhesion assays revealed that both adult and neonatal keratinocytes demonstrated increased attachment to Col I and III in the presence of recombinant VCAN and LUM. VCAN and LUM also provided a pro-proliferative signal to both adult and neonatal keratinocytes both in the presence and absence of Col I & III in vitro. Interestingly, our data suggest that the G1 domain of VCAN alone promotes keratinocyte adhesion and proliferation consistent with previous literature describing that this domain enhances fibroblast adhesion and proliferation2. Further we were able to demonstrate that recombinant VCAN improved the skin tissue regenerative potential of adult human keratinocytes in 3D organotypic cultures. These data suggest that changes in proteoglycans deposited in the dermis or microenvironment of ageing skin epidermal cells, particularly decreased VCAN, may contribute to the poorer ability of adult keratinocytes to regenerate epidermal tissue. Thus, skin ageing is also a function of the extrinsic cellular and molecular microenvironment of which dermal pericytes are an important component.