I. Fibroblasts (also see post “The Role of Fibroblasts In Skin Aging“)

1. Fibroblast senescence (fibroblast aging)
   • aged fibroblast – senescent fibroblasts were observed to accumulate with age
   • decreased synthesis and secretion of extracellular matrix components (e.g. collagen, elastin, ground substances)
   • differential expression of genes involved in skin aging
     • increased matrix metalloproteinases (MMP) and decreased tissue inhibitors of metalloproteinase (TIMP).
     • growth factors ( increased keratinocyte growth factor (KGF) and vascular endothelial growth factor (VEGF))
     • inflammatory cytokines or proinflammatory mediators
       • monocyte chemoatractant protein 1 (MCP-1) secretion reduced
   • col­lagen lattice contraction capacity increases for papillary fibroblast
2. Morphologically altered fibroblasts (collapsed instead of stretched) prevent it from receiving mechanical information from collagen fibers

II Extracellular Matrix

1. Collagen (Collagen fibers primarily composed of collagen I and/or collagen III) (see post “Types of Collagen In Skin Layer And In Skin Aging”)
   • decreased new collagen synthesis
   • increased collagen degradation (collagen fragmentation) by MMP – collagen fragments further inhibit fibroblast function with reduced synthesis of matrix components.
   • increased collagen damage (protein crosslinking via glycation)
   • histological changes: Collagen fiber bundles are shorter and thinner and have more space between the fiber bundles. The collagen bundles have a disorganized appearance with “tangled” fibers running in all directions. Cells imbedded in the collagen matrix have a rounded appearance and many of the cells appear to be separated from the surrounding collagen altogether.
2. Elastin (The Elastic System of Skin)
   • decreased new elastin and fibrillin synthesis
   • increased elastin degradation by MMP (elastosis); elastosis is especially pronounced in photodamaged skin (solar elastosis)
   • increased elastin damage (protein crosslinking via glycation)
3. Ground Substances
   • decreased glycosoaminoglycans – decreased water retention ability
   • decreased chondroitin sulfate