Aspartic acid racemization: evidence for marked longevity of elastin in human skin

Ritz‐Timme, Stefanie; Laumeier, Inga; Collins, Matthew J.

doi:10.1111/j.1365-2133.2003.05618.x

Cited by 140 publications

(122 citation statements)

References 50 publications

(95 reference statements)

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“…From these studies, and from previous work in the rat, it was estimated that rodent arterial elastin, with a half-life of 27-40 years (Davis 1993;Rucker and Tinker 1977), has an expected longevity many times greater than the longevity of the host organism. AAR studies in humans indicate that aortic elastin is much more metabolically stable than the fibrillar collagens (Powell et al 1992) and that elastin in skin, although not replaced, may undergo age-related damage (Ritz-Timme et al 2003). The most compelling evidence for elastic fibre longevity in a human tissue was presented by Shapiro and coworkers (Shapiro et al 1991).…”

Section: Structure and Functionmentioning

confidence: 99%

Tissue elasticity and the ageing elastic fibre

Sherratt

2009

AGE

265

189

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The ability of elastic tissues to deform under physiological forces and to subsequently release stored energy to drive passive recoil is vital to the function of many dynamic tissues. Within vertebrates, elastic fibres allow arteries and lungs to expand and contract, thus controlling variations in blood pressure and returning the pulmonary system to a resting state. Elastic fibres are composite structures composed of a cross-linked elastin core and an outer layer of fibrillin microfibrils. These two components perform distinct roles; elastin stores energy and drives passive recoil, whilst fibrillin microfibrils direct elastogenesis, mediate cell signalling, maintain tissue homeostasis via TGFβ sequestration and potentially act to reinforce the elastic fibre. In many tissues reduced elasticity, as a result of compromised elastic fibre function, becomes increasingly prevalent with age and contributes significantly to the burden of human morbidity and mortality. This review considers how the unique molecular structure, tissue distribution and longevity of elastic fibres pre-disposes these abundant extracellular matrix structures to the accumulation of damage in ageing dermal, pulmonary and vascular tissues. As compromised elasticity is a common feature of ageing dynamic tissues, the development of strategies to prevent, limit or reverse this loss of function will play a key role in reducing age-related morbidity and mortality.

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Section: Structure and Functionmentioning

confidence: 99%

Tissue elasticity and the ageing elastic fibre

Sherratt

2009

AGE

265

189

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“…Production of elastin reaches its highest levels in the third trimester of the fetal life and steadily decreases during early postnatal development (11,12). In undisturbed tissues, elastic fibers may last over the entire human lifespan (13,14).The net deposition of elastin appears to be controlled on both the transcriptional level (tropoelastin mRNA message expression (15, 16)) and-post-transcriptional level (tropoelastin message stability (17-19)). There are also several other post-transcriptional events, which control secretion of tropoelastin monomers and their proper extracellular assembly (20, 21) and regulate the cross-linking of tropoelastin into the polymeric "insoluble" elastin, the most durable element of the extracellular matrix (14).…”

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confidence: 99%

Fluctuations of Intracellular Iron Modulate Elastin Production

Bunda

Kaviani

Hinek

2005

Journal of Biological Chemistry

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Production of insoluble elastin, the major component of elastic fibers, can be modulated by numerous intrinsic and exogenous factors. Because patients with hemolytic disorders characterized with fluctuations in iron concentration demonstrate defective elastic fibers, we speculated that iron might also modulate elastogenesis. In the present report we demonstrate that treatment of cultured human skin fibroblasts with low concentration of iron 2-20 M (ferric ammonium citrate) induced a significant increase in the synthesis of tropoelastin and deposition of insoluble elastin. Northern blot and realtime reverse transcription-PCR analysis revealed that treatment with 20 M iron led to an increase of ϳ3-fold in elastin mRNA levels. Because treatment with an intracellular iron chelator, desferrioxamine, caused a significant decrease in elastin mRNA level and consequent inhibition of elastin deposition, we conclude that iron facilitates elastin gene expression. Our experimental evidence also demonstrates the existence of an opposite effect, in which higher, but not cytotoxic concentrations of iron (100 -400 M) induced the production of intracellular reactive oxygen species that coincided with a significant decrease in elastin message stability and the disappearance of iron-dependent stimulatory effect on elastogenesis. This stimulatory elastogenic effect was reversed, however, in cultures simultaneously treated with high iron concentration (200 M) and the intracellular hydroxyl radical scavenger, dimethylthiourea. Thus, presented data, for the first time, demonstrate the existence of two opposite iron-dependent mechanisms that may affect the steady state of elastin message. We speculate that extreme fluctuations in intracellular iron levels result in impaired elastic fiber production as observed in hemolytic diseases.Mature elastic fibers and laminae provide extensibility and elastic recoil to vascular walls and ligaments and form a connective tissue framework of lungs, elastic cartilage, and skin (1, 2). They are complex structures made of polymeric (insoluble) elastin and 12-nm microfibrils that consist of several glycoproteins, e.g. fibrillins, fibulins, and microfibril-associated glycoproteins (3-6). Elastic fiber formation (elastogenesis) is a complex process involving several intracellular and extracellular events. Cells (fibroblasts, endothelial cells, chondroblasts, or vascular smooth muscle cells) must first synthesize and secrete numerous glycoproteins to form a microfibrillar scaffold upon which tropoelastin, the precursor peptides, are properly assembled and covalently cross-linked by lysyl oxidase into a resilient polymer, insoluble elastin (7-10). Production of elastin reaches its highest levels in the third trimester of the fetal life and steadily decreases during early postnatal development (11,12). In undisturbed tissues, elastic fibers may last over the entire human lifespan (13,14).The net deposition of elastin appears to be controlled on both the transcriptional level (tropoelastin mRNA message express...

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“…For example, type-1 collagen in human skin has an estimated half-life of 15 years [19]. Elastins in human skin also have marked longevity [20]. The cumulative effect of modification of ECM proteins results in altered functionality, as observed in DM and elderly.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of aging, diabetes mellitus, and skin wounds by scanning acoustic microscopy with protease digestion

Miura

Yamashita

2018

Pathobiology of Aging & Age-related Diseases

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Scanning acoustic microscopy (SAM) can assess tissue stiffness by calculating the speed of sound (SOS) through tissues. SOS increases as tissue stiffness increases. Sensitivity to protease digestion depends on protein type, concentration, and modification. We analyzed the SOS images of formalin-fixed paraffin-embedded skin sections from elderly, young, diabetic, and nondiabetic subjects, as well as chronic and acute wounds. SAM provided high-resolution histology similar to LM and revealed characteristic SOS alteration following pepsin treatment. SOS values of dermis samples from elderly subjects (especially females) were lower than those of younger adults, which was indicative of age-related dermal softening and loosening. SOS values of elderly females were lower than those of younger females and elderly males. Dermal SOS showed a positive correlation with epidermal thickness. SOS values of epidermis of elderly subjects were higher than those of younger adults and showed a rapid decline 0.5h after protease digestion. Reticular dermis of diabetic patients exhibited greater pepsin resistance than that of nondiabetic patients. Chronic wounds exhibited greater SOS values and pepsin resistance than acute wounds. SOS variation with aging, diabetes mellitus, and wound fibrosis reflected histological and mechanical changes associated with senescence and disease duration. Epidermal thickness reflects age-related changes in dermal stiffness.

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Aspartic acid racemization: evidence for marked longevity of elastin in human skin

Abstract: The age-dependent accumulation of modified aspartic acid residues appears to be a common feature in ageing elastin, independent of the tissue source. This indicates a lack of turnover and an accumulation of elastin damage in diverse ageing tissues, possibly as part of programmed ageing.

Cited by 140 publications

References 50 publications

Tissue elasticity and the ageing elastic fibre

Tissue elasticity and the ageing elastic fibre

Fluctuations of Intracellular Iron Modulate Elastin Production

Evaluation of aging, diabetes mellitus, and skin wounds by scanning acoustic microscopy with protease digestion

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