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Looking Older

Looking Older SPECIAL ARTICLE Fibroblast Collapse and Therapeutic Implications Gary J. Fisher, PhD; James Varani, PhD; John J. Voorhees, MD kin appearance is a primary indicator of age. During the last decade, substantial progress has been made toward understanding underlying mechanisms of human skin aging. This understanding provides the basis for current use and new development of antiaging treat- S ments. Our objective is to review present state-of-the-art knowledge pertaining to mecha- nisms involved in skin aging, with specific focus on the dermal collagen matrix. A major feature of aged skin is fragmentation of the dermal collagen matrix. Fragmentation results from actions of specific enzymes (matrix metalloproteinases) and impairs the structural integrity of the dermis. Fibroblasts that produce and organize the collagen matrix cannot attach to fragmented collagen. Loss of attachment prevents fibroblasts from receiving mechanical information from their sup- port, and they collapse. Stretch is critical for normal balanced production of collagen and collagen- degrading enzymes. In aged skin, collapsed fibroblasts produce low levels of collagen and high levels of collagen-degrading enzymes. This imbalance advances the aging process in a self- perpetuating, never-ending deleterious cycle. Clinically proven antiaging treatments such as topi- cal retinoic acid, carbon dioxide laser resurfacing, and http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Dermatology American Medical Association

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Publisher
American Medical Association
Copyright
Copyright 2008 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.
ISSN
2168-6068
eISSN
2168-6084
DOI
10.1001/archderm.144.5.666
pmid
18490597
Publisher site
See Article on Publisher Site

Abstract

SPECIAL ARTICLE Fibroblast Collapse and Therapeutic Implications Gary J. Fisher, PhD; James Varani, PhD; John J. Voorhees, MD kin appearance is a primary indicator of age. During the last decade, substantial progress has been made toward understanding underlying mechanisms of human skin aging. This understanding provides the basis for current use and new development of antiaging treat- S ments. Our objective is to review present state-of-the-art knowledge pertaining to mecha- nisms involved in skin aging, with specific focus on the dermal collagen matrix. A major feature of aged skin is fragmentation of the dermal collagen matrix. Fragmentation results from actions of specific enzymes (matrix metalloproteinases) and impairs the structural integrity of the dermis. Fibroblasts that produce and organize the collagen matrix cannot attach to fragmented collagen. Loss of attachment prevents fibroblasts from receiving mechanical information from their sup- port, and they collapse. Stretch is critical for normal balanced production of collagen and collagen- degrading enzymes. In aged skin, collapsed fibroblasts produce low levels of collagen and high levels of collagen-degrading enzymes. This imbalance advances the aging process in a self- perpetuating, never-ending deleterious cycle. Clinically proven antiaging treatments such as topi- cal retinoic acid, carbon dioxide laser resurfacing, and

Journal

JAMA DermatologyAmerican Medical Association

Published: May 1, 2008

References