Decline of fibroblast chemotaxis with age of donor and cell passage number.

Human dermal fibroblasts have a limited life span in culture, which is manifested by a progressive decline of their proliferative activity. Here we show by the Boyden Chamber assay that the chemotactic response of human fibroblasts to fibroblast-conditioned medium and fibronectin declines during cellular aging in vitro and in vivo. The chemotactic response of human embryonic fibroblasts (HEF) declined progressively after the 25th passage. Virtually no chemotactic activity could be observed after the 40th passage in culture. Fibroblasts cultures from donors aged between 70-90 years had lost chemotactic activity by the 15th passage. Cells from patients suffering from progeroid syndromes of premature aging showed, even in early passages, a very low chemotactic response (20% of the HEF) and lost their chemotactic activity after a few subcultures. The response to the chemoattractant fibronectin also decreased with aging. Immunofluorescence studies indicated that the decline in chemotactic activity was accompanied by the formation of a thicker fibronectin network in the extracellular matrix of senescent human fibroblasts and progeroid cells than that observed in early passage embryonic cultures. Since fibroblast chemotaxis and synthesis of connective tissue components probably play an important role in tissue repair, our results could contribute to an understanding of age-related differences in the healing of skin wounds.