Lab Anim Res.  2011 Mar;27(1):1-8. 10.5625/lar.2011.27.1.1.

Molecular Mechanisms and In Vivo Mouse Models of Skin Aging Associated with Dermal Matrix Alterations

• Hwang KA
• Yi BR
• Choi KC

• KMID: 2391851
• DOI: http://doi.org/10.5625/lar.2011.27.1.1

Abstract

Skin is the most superficial body organ and plays an important role in protecting the body from environmental damage and in forming social relations. With the increase of the aging population in our society, dermatological and cosmetic concerns of skin aging are rapidly increasing. Skin aging is a complex process combined with intrinsic and extrinsic factors. Intrinsic or chronological skin aging results from the passage of time and is influenced by genetic factors. Extrinsic skin aging is mainly determined by UV irradiation, also called photoaging. These two types of aging processes are superimposed on sun-exposed skin, and have a common feature of causing dermal matrix alterations that mostly contribute to the formation of wrinkles, laxity, and fragility of aged skin. The dermal matrix contains extracellular matrix proteins such as collagen, elastin, and proteoglycans that confer the strength and resiliency of skin. Skin aging associated with dermal matrix alterations and atrophy can be caused by cellular senescence of dermal cells like fibroblasts, and decreased synthesis and accelerated degradation of dermal matrix components, especially collagen fibers. Both intrinsic aging and photoaging exert influence during each step of dermal matrix alteration via different mechanisms. Mouse models of skin aging have been extensively developed to elucidate intrinsic aging and photoaging processes, to validate in vitro biochemical data, and to test the effects of pharmacological tools for retarding skin aging because they have the advantages of being genetically similar to humans and are easily available.

Keyword

Intrinsic skin aging; photoaging; dermal matrix alterations; collagen; mouse model

MeSH Terms

Aging
Animals
Atrophy
Cell Aging
Collagen
Cosmetics
Elastin
Extracellular Matrix Proteins
Fibroblasts
Humans
Mice
Proteoglycans
Skin
Skin Aging
Collagen
Cosmetics
Elastin
Extracellular Matrix Proteins
Proteoglycans

Figure

• 

  Figure 1 Common mechanism of type I collagen alteration for intrinsic aging and photoaging in dermal connective tissue. Intrinsic aging induces the down-regulation of transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF) in the TGF-β/Smad/CTGF/procollagen axis and leads to decreased synthesis of type I collagen. In photoaging, UV irradiation from the sun generates reactive oxygen species (ROS) which activate growth factor and cytokine receptors on fibroblasts in the skin. Activated receptors stimulate p38 and JNK, members of the MAPK signaling cascade, and c-Fos and c-Jun subsequently combine to form AP-1 which stimulates matrix metalloproteinase (MMP) transcription. Increased MMP transcription accelerates the degradation of collagen which induces dermal matrix alterations. ROS generation and AP-1 formation induced by photoaging can also lead to decreased collagen synthesis by blocking TGF-β type II receptor/Smad signaling. ROS can also be generated from oxidative metabolism and accumulate during the intrinsic aging process.

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