The impaired wound healing associated with aging may reflect inadequate secretion or delivery of
cytokines. Transforming growth factor-beta(1) is a mitogenic
polypeptide with beneficial effects on wound healing. In the present study we questioned whether
topical administration of transforming growth factor-beta(1) could improve the wound healing process in aged rats in vivo.
Wound repair (from 1 to 14 days) was analyzed in full-thickness incisional
wounds from 2-year-old rats with or without a single topical application of transforming growth factor-beta(1) (1 microg/
wound) at the time of wounding. Identical
wounds from 3-month-old, untreated rats served as controls. Histologic analysis showed a marked delay in several aspects of
wound repair in the aged rats in comparison with that noted in the younger animals. Immunostaining of the
wounds for
proliferating cell nuclear antigen showed a reduction in the number of cycling fibroblasts in old rats. In addition, the number of capillaries per unit area of the
wound as determined by a
stain for
Griffonin (
Bandeiraea) simplicifolia lectin, and the number of inflammatory cells as identified by an antibody specific for macrophages, were also reduced in the
wound area in old rats. Treatment with transforming growth factor-beta(1) resulted in marked enhancement of the following parameters: cell proliferation, inflammatory cell and fibroblast influx,
wound closure, and angiogenesis. As seen with in situ hybridization, a similar temporal pattern of expression of messenger RNAs corresponding to
type I procollagen and Secreted
Protein, Acidic and Rich in
Cysteine (
osteonectin), known to be prevalent in healing
wounds, was observed in both young and aged rats. However, the levels of
mRNA corresponding to these secreted
proteins appeared to be reduced in
wound tissue from aged rats. Treatment with transforming growth factor-beta(1) subsequently resulted in an increase in the expression of both
type I procollagen and Secreted
Protein, Acidic and Rich in
Cysteine mRNA in the
wound tissue from aged rats. In summary, a single topical application of transforming growth factor-beta(1) to the
wounds of aged rats at the time of wounding was associated with a healing response that, in all the parameters of
wound repair examined, was similar to that of young rats. Topical transforming growth factor-beta(1) might therefore be beneficial in the treatment of dermal
wounds in the aged.