Vitamin A Antagonizes Decreased Cell Growth and Elevated Collagen-Degrading Matrix Metalloproteinases and Stimulates Collagen Accumulation in Naturally Aged Human Skin1

Abstract

Damage to human skin due to ultraviolet light from the sun (photoaging) and damage occurring as a consequence of the passage of time (chronologic or natural aging) are considered to be distinct entities. Photoaging is caused in part by damage to skin connective tissue by increased elaboration of collagen-degrading matrix metalloproteinases, and by reduced collagen synthesis. As matrix metalloproteinase levels are known to rise in fibroblasts as a function of age, and as oxidant stress is believed to underlie changes associated with both photoaging and natural aging, we determined whether natural skin aging, like photoaging, gives rise to increased matrix metalloproteinases and reduced collagen synthesis. In addition, we determined whether topical vitamin A (retinol) could stimulate new collagen deposition in sun-protected aged skin, as it does in photoaged skin. Sun-protected skin samples were obtained from 72 individuals in four age groups: 18-29 y, 30-59 y, 60-79 y, and 80+ y. Histologic and cellular markers of connective tissue abnormalities were significantly elevated in the 60-79 y and 80+ y groups, compared with the two younger age groups. Increased matrix metalloproteinase levels and decreased collagen synthesis/expression were associated with this connective tissue damage. In a separate group of 53 individuals (80+ y of age), topical application of 1% vitamin A for 7 d increased fibroblast growth and collagen synthesis, and concomitantly reduced the levels of matrix-degrading matrix metalloproteinases. Our findings indicate that naturally aged, sun-protected skin and photoaged skin share important molecular features including connective tissue damage, elevated matrix metalloproteinase levels, and reduced collagen production. In addition, vitamin A treatment reduces matrix metalloproteinase expression and stimulates collagen synthesis in naturally aged, sun-protected skin, as it does in photoaged skin.

Inhibition of Type I Procollagen Synthesis by Damaged Collagen in Photoaged Skin and by Collagenase-Degraded Collagen in Vitro

“…7,8 This is also in contrast to findings in natural aging, where a higher level of collagenase was observed in sun-protected skin from Ͼ80-year-old individuals than in sun-protected skin of younger (18-to 29-year-old) individuals. 42 Because dermal fibroblasts do not seem to be intrinsically damaged in severely photoaged skin, it follows that inhibitory influences within the in vivo environment of severely photodamaged skin may act in some way to prevent cells that are inherently capable of elaborating collagen from doing so. In vitro studies performed with intact and partially degraded collagen gels support this suggestion.…”

Collagen expression in fibroblasts with a novel LMNA mutation

“…Reduced production of type I and III collagens has been described in primary fibroblasts derived from the aged skin [30,31]. These changes are associated with an increased expression of matrix metalloproteinase and a reduced expression of tissue inhibitor of metalloproteinases in skin samples from aged people [32]. Such findings were also reported in dermal fibroblasts that underwent senescence in culture [33].…”

Anti-Aging Cosmetics Approaches and Components in Products

“…Güçlü bir antioksidandır. Kollajen sentezini arttırıp kollejenaz etkisini azaltabilirler 49,50 . Retinol üzerinde yapılan in vitro ve in vivo çalışmalarda sert ve kuru cilt üzerinde kollajen ve glikozaminoglikan sentezini artırdığı, hücre rejenerasyonunu olumlu yönde değiştirdiği, epitel dokunun korunmasında etkili olduğu belirtilmiştir 10,46 .…”