title: Vitamin A antagonizes decreased cell growth and elevated collagen-degrading matrix metalloproteinases and stimulates collagen accumulation in naturally aged human skin.
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.
authors.affiliation: Departments of Pathology and Dermatology, The University of Michigan, Medical School, Ann Arbor, MI 48109, USA. varani@umich.edu
authors.forename: J
authors.initials: J
authors.lastname: Varani
authors.forename: R L
authors.initials: RL
authors.lastname: Warner
authors.forename: M
authors.initials: M
authors.lastname: Gharaee-Kermani
authors.forename: S H
authors.initials: SH
authors.lastname: Phan
authors.forename: S
authors.initials: S
authors.lastname: Kang
authors.forename: J H
authors.initials: JH
authors.lastname: Chung
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Wang
authors.forename: S C
authors.initials: SC
authors.lastname: Datta
authors.forename: G J
authors.initials: GJ
authors.lastname: Fisher
authors.forename: J J
authors.initials: JJ
authors.lastname: Voorhees
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D003094:Collagen / Q000378:metabolism* / Q000494:pharmacology; D003238:Connective Tissue / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D020782:Matrix Metalloproteinases / Q000187:drug effects; D008875:Middle Aged; D011347:Procollagen / Q000096:biosynthesis; D012867:Skin / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D015595:Skin Aging / Q000187:drug effects* / Q000502:physiology; D013268:Stimulation, Chemical; D014801:Vitamin A / Q000494:pharmacology*
chemical_list: D011347:Procollagen; D014801:Vitamin A; D003094:Collagen; D020782:Matrix Metalloproteinases