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Fibroblast Cells Physiological Changes

Role Of Fibroblasts In Aging Stroma

The role of fibroblasts in aging tissue has been most extensively studied in mammalian skin. The skin is composed of two primary layers: the epidermis, which contains the major epithelial cells of the skin (epidermal keratinocytes), and the dermis, which is the stromal layer of the skin. As with other stroma, the dermis is maintained in large part by fibroblasts, which secrete dermal collagens, elastin, and other extracellular matrix components. When the skin is wounded, fibroblasts secrete proteases to degrade the wounded matrix, and then synthesize new matrix. The fibroblasts also secrete growth factors to stimulate the keratinocytes to proliferate and close the wound and cytokines to attract macrophages to engulf and degrade debris.

Young skin is characterized by thick epidermal and dermal layers and relatively efficient wound healing. The epidermis contains numerous invaginations, or rete ridges, and the dermis contains dense collagen. Old skin, by contrast, is characterized by a thinner epidermis that contains fewer and shallower rete ridges. The dermis also becomes thinner, showing a marked loss of collagen and other fibers. Changes in the dermis are in large measure responsible for the loss of elasticity and wrinkling that is the hallmark of aging skin. In addition, wound healing slows with age. Aging is particularly sensitive to environmental influence in the skin: skin exposed to the sun (ultraviolet light) ages much more rapidly than sun-protected skin.

As discussed above, senescent fibroblasts appear to increase with age in human dermis, and senescent fibroblasts constitutively secrete factors that, ordinarily, are secreted only transiently during wound healing. These factors include interstitial collagenase and elastase, which are matrix metalloproteinases that degrade dermal collagens and elastin. Ultraviolet light can also induce these metalloproteinases, as well as cellular senescence, in fibroblasts. Thus, some of the hallmarks of aging skin, such as wrinking and loss of dermal elasticity, are likely due, at least in part, to the secretion of metalloproteinases by fibroblasts, which, in turn, may be due to cellular senescence and/or environmental exposure to ultraviolet light. Senescent and ultraviolet-damaged fibroblasts also secrete enzymes that degrade the basement membrane, the dense matrix onto which the epithelial cells are organized. This may contribute to the age-dependent thinning of the epidermis and the loss of rete ridges, as the basement membrane is critically important for the proper organization and function of epithelial cells.

Age-dependent changes in fibroblast physiology may also contribute to the increased incidence of cancer that is a hallmark of mammalian aging. Several lines of evidence suggest mutations and loss of normal tissue structure synergize to generate the exponential rise in cancer that occurs with age. Tissue structure and integrity are critically dependent on an intact stromal and basement membrane, both of which are disrupted by senescent or damaged fibroblasts. In addition, senescent fibroblasts secrete epithelial growth factors, which can stimulate the growth of epithelial cells that have acquired potentially oncogenic mutations.

In summary, fibroblasts undergo physiological changes with age. These changes are induced by environmental and intrinsic factors, and disrupt the integrity of the stroma and basement membrane. Both these structures are critical in order for epithelial cells, and hence tissues, to carry out their normal functions. These structures are also important for suppressing the progression of cancer.



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Additional topics

Medicine EncyclopediaAging Healthy - Part 3Fibroblast Cells Physiological Changes - Fibroblasts In Vivo, Fibroblasts In Culture, The Senescent Phenotype, Causes Of The Senescence Response