Molecular Mechanisms andIn VivoMouse Models of Skin Aging Associated with Dermal Matrix Alterations

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.

One week’s holiday sun exposure induces expression of photoaging biomarkers

“…Ultraviolet radiation activates cytokines and growth factors, and also disturbs the TGF-b/Smad signaling pathway. This results from the reduced expression of TbRII receptor and the induction of Smad7 proteins, leading in consequence to the inhibition of the TGF-b/Smad2/3 pathway, its translocation to the nucleus, and the generation of the Smad/DNA complex [20][21]. These data are in line with our observations.…”

Rat skin physiology is modified by age

“…Duas áreas opostas (2cm , uma próxima do pescoço e outra próxima da cauda) foram selecionadas no dorso do animal após remoção mecânica dos pêlos (24 horas antes do inicio do estudo). Os parâmetros avaliados incluíram a Perda Transepidérmica de Água (PTEA), através do Tewameter® TM300 (CK electronics, Germany), 2 expressa em g/m /h; a hidratação superficial epidérmica medida através do MoistureMeter® SC (Delphin, Kuopio, Finland), expressa em unidades arbitrárias (UA); e medida biomecânica através do Cutometer® sistema MPA80, equipado com uma sonda de 8mm de diâmetro, e do Reviscometer® sistema RVM600, ambos da Courage-Khazaka, Cologne, Germany. As medições foram realizadas diariamente por um período de cinco dias (D1-D5).…”

“…Animal experimentation was conducted in accordance with the relevant Community and National rules on animal protection for experimental and other scientific purposes. The animals were sedated with inhaled ethyl ether (7ml embedded in the Introdução O envelhecimento é um processo complexo que afeta todas as espécies, tem sido extensivamente estudado e atualmente é alvo de investigação na área de geriatria [1,2 ] . No que diz respeito aos seres humanos, é claro que a raça/etnia, as variações intrínsecas das diferentes regiões anatómicas e as alterações neuro-hormonais [3] são as principais determinantes e a derme é vista como o alvo principal.…”

“…It has been extensively studied and geriatrics is currently [1,2] a target for research . With regard to humans, it is clear that race/ethnicity, the intrinsic variations of different anatomical regions and the neuro-hormonal [3] control are main determinants and the dermis is perceived to be the main target.…”

The in vivo effect of L-arginine on skin elasticity in mice

“…Like all organs, skin undergoes chronological aging, but unlike others, it is in direct contact with the environment, and therefore further ages as a result of environmental damage (Fisher et al, 2002;Pageon et al, 2007;Hwang, Yi, Choi, 2011;Levakov et al, 2012). The aging of human skin is a complex process, induced by both intrinsic factors resulting from tissue degeneration that are largely genetically determined, and by extrinsic factors caused by environmental exposure, predominantly including ultraviolet radiation, smoking, excessive alcohol drinking, and malnutrition.…”