Vitamin A antagonizes decreased cell growth and elevated collagen-degrading matrix metalloproteinases and stimulates collagen accumulation in naturally aged human skin

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 n atural aging) are considered to be distinct entities. Photoaging is caused in part by damage to skin connective tissue by increased elaboration of col lagen-degrading matrix metalloproteinases, and by reduced collagen synthesi s. As matrix metalloproteinase levels are known to rise in fibroblasts as a function of age, and as oxidant stress is believed to underlie changes ass ociated with both photoaging and natural aging, we determined whether natur al skin aging, like photoaging, gives rise to increased matrix metalloprote inases and reduced collagen synthesis. In addition, we determined whether t opical vitamin A (retinol) could stimulate new collagen deposition in sun-p rotected aged skin, as it does in photoaged skin. Sun-protected skin sample s were obtained from 72 individuals in four age groups: 18-29 y, 30-59 y, 6 0-79 y, and 80+ y. Histologic and cellular markers of connective tissue abn ormalities were significantly elevated in the 60-79 y and 80+ y groups, com pared with the two younger age groups. Increased matrix metalloproteinase l evels 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 grow th and collagen synthesis, and concomitantly reduced the levels of matrix-d egrading matrix metalloproteinases. Our findings indicate that naturally ag ed, sun-protected skin and photoaged skin share important molecular feature s including connective tissue damage, elevated matrix metalloproteinase lev els, and reduced collagen production. In addition, vitamin A treatment redu ces matrix metalloproteinase expression and stimulates collagen synthesis i n naturally aged, sun-protected skin, as it does in photoaged skin.