Evidence that filopodia outgrowth is a common final pathway for fibroblast growth inhibition in vitro.

To identify events associated with fibroblast growth inhibition, the effect of two known inhibitors, interferon-alpha and all-trans retinoic acid, on the growth and surface morphology of cultured fibroblasts was examined. Interferon-alpha administered at seeding reduced both growth rate and saturation density; all-trans retinoic acid reduced only saturation density. However, both negative growth modulators were associated with an increase in filopodia outgrowth and an increase in intracellular filamentous actin in a time course corresponding to onset of growth inhibition by these agents.

Effect of donor age and prior sun exposure on growth inhibition of cultured human dermal fibroblasts by all trans-retinoic acid.

The effect of retinoic acid on human fibroblasts was studied in a cell culture model of chronologic aging and photoaging. During early exponential phase, all trans-retinoic acid significantly stimulated growth rate of adult arm-derived dermal fibroblasts but not of newborn or adult foreskin-derived fibroblasts. Retinoic acid also significantly reduced saturation density in most young adult arm-derived lines and all 24 lines derived from old adult arm and foreskin.

In-vitro studies of aging.

Research has conclusively established that normal diploid cells in culture have a limited replicative life span, and that cells from adult organisms have a shorter life span than cells from young organisms or embryos. Although it is unlikely that death of the organism is caused by failure in cellular proliferative capacity, the changes that accompany alterations in proliferative capacity may play significant roles in organismic aging. The causes of the decreased proliferative vigor of cells with age are not known, but one factor may reside in the fact that with increasing in-vitro or donor age, cells become less able to respond to mitogens.

An extract of bovine thymus stimulates human keratinocyte growth in vitro.

An extract prepared from newborn calf thymus stimulated proliferation of human keratinocytes cultured from newborn foreskins and from skin biopsies of 26 adult volunteers aged 19 to 70 years. Growth over the 7-day assay period in the basal medium was age-dependent, with newborn cultures achieving a 10-fold increase in cell number over seeding density, old adult cultures barely maintaining their seeding density and young adult cultures intermediate in proliferative capacity. Maximally stimulatory extract concentration was 5-fold higher for newborn than for adult keratinocytes, with adult cultures experiencing toxicity at doses still growth-promoting for newborn cultures.

Autocrine growth stimulation of human keratinocytes by epidermal cell-derived thymocyte-activating factor: implications for skin aging.

The monocyte-derived cytokine interleukin-1 (IL-1) has growth-promoting activity for a variety of cell types, including lymphocytes and fibroblasts. We have previously shown that the epidermal cell-derived thymocyte-activating factor (ETAF) strongly resembles IL-1 in terms of biological, biochemical, and molecular biological properties. Because some lymphokines are known ot alter epidermal cell growth and differentiation and because cultured epidermal keratinocytes are capable of autocrine growth stimulation in vitro through "conditioning" of their culture medium, we sought to evaluate the effect of ETAF on keratinocyte growth.