Articulo sobre la piel. envejecimiento (1)

Age-Related Tissue Stiffening: Cause and Effect Michael J. Sherratt * Manchester Academic Health Sciences Centre and School of Regenerative Biomedicine, Faculty of Medical and Human Sciences, The University of Manchester, Manchester, United Kingdom. Significance: Tissue elasticity is severely compromised in aging skin, lungs, and blood vessels. In the vascular and pulmonary systems, respectively, loss of mechanical function is linked to hypertension, which in turn is a risk factor for heart and renal failure, stroke, and aortic aneurysms, and to an increased risk of mortality as a result of acute lung infections. Recent Advanc es: Alt hou gh cellular mec han isms were thought to play an important role in mediating tissue aging, the reason for the apparent sensi- tivity of elastic fibers to age-related degradation remained unclear. We have recently demonstrated that compared with type I collagen, a key component of the ela sti c fiber system, the cys tei ne- rich fibr ill in mic rofi bri l is hig hly susc eptib le to direc t UV expos ure in a cell- free environ ment. We hypothe- sized therefore that, as a consequence of both their remarkable longevity and cysteine- rich comp ositi on, many elast ic fiber -associat ed componen ts will be susceptible to the accumulation of damage by both direct UV radiation and reactive oxygen species-mediated oxidation. Critical Issues: Although elastic fiber remodeling is a common feature of aging dynamic tissues, the inaccessibility of most human tissues has hampered at- tempts to define the molecular causes. Clini cal Care Relev ance: Alth ough , curre ntly, the locali zed repai r of damag ed ela stic fibe rs ma y be eff ect ed by the topic al appl ica tion of ret ino ids and som e cosmetic products, future studies may extend the application of systemic transforming growth factor b antagonists, which can prevent cardiovascular remodeling in murine Marfan syndrome, to aging humans. Acellular mechanisms may be key mediators of elastic fiber remodeling and hence age-related tissue stiffening. SCOPE The components of skin, bl oo d vess els, and lung s are requ ired to with stan d diver se mech anic al envi - ronments. Skin, for example, is sub- ject ed to cont inuo us stresses , whic h act in multiple directions, 1 but major arteries must resist and dampen cy- clic variations in blood pressure. 2 De- spite thes e diss imilar phys iolo gical requ irements , the mech anic al prop - erti es of most soft biol ogic al tiss ues are domina ted by an extrac ell ula r matrix (ECM) in which fibrillar colla- gens and hydrated proteoglycans re- sis t ten sil e and compress ive forces and elastic fibers confer both compli- an ce an d pa ss iv e re co il . Al th ou gh elas tic fiber s are comp lex mult icom- ponent assemblies, their structure is dominated by two major constituents: hi gh ly cr os sl in ke d el as ti n, a mo - lec ula r spr ing tha t stores and the n rele ases mechan ical ener gy, and fibr ill in mic rofi bri ls, wh ich for m the int erf ac e be twe en th e ela sti c fibe r and the surr ound ing tissue. 3 Th ese mi- crofibrils perform multiple physiolog- ic al fu nc tions by acti ng as (i ) an imp ortan t tissue rep os ito ry for cel l signaling molecules, (ii) the adhesive int erf ac e be twe en the ela sti c fibe r and Michael J. Sherratt, BSc, MSc, PhD Submitted for public ation July 25, 2011. *Corr espond ence: Manch ester Acade mic Hea lth Sci enc es Cen tre and Sch ool of Re- genera tive Biomedicin e, Faculty of Medical and Human Sciences, The University of Manchester, 1st Floor Stopford Building, Oxford Road, Man- cheste r M13 9PT, Uni ted Kingdom (e- mail: [email protected]). Abbreviations and Acronyms AFM = atomic force microscope (microscopy) DEJ = dermal-epidermal junction ECM = extracellular matrix LTBP = latent transforming growth factor b binding protein MMP = matrix metalloproteinase ROS = reactive oxygen species TGF-b = transforming growth factor b UVR = ultraviolet radiation j 11 ADVANCES IN WOUND CARE, VOLUME 2, NUMBER 1 Copyright ª 2013 by Mary Ann Liebert, Inc. DOI: 10.1089/wound.2011.0328

Articulo sobre la piel. envejecimiento (1)

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