Aspartic Acid Racemization in Intervertebral Discs as an Aid to Postmortem Estimation of Age at Death

Ritz, S.; Schütz, H. W.

doi:10.1520/jfs13449j

Cited by 49 publications

(28 citation statements)

References 22 publications

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“…tion has also been studied in the acid-soluble and -insoluble collagen-rich fraction of human rib cartilage (19) and in the nucleus pulposus and annulus fibrosis from the intervertebral disc (21). In these studies, estimated aspartic acid racemization rates in cartilagenous tissues were 4 -10-fold higher (0.108 -0.236% D-Asp per year (19,21)) than our estimation for cartilage collagen (0.0258% D-Asp per year). Unfortunately, the protocols used in these studies result in significant amounts of residual proteoglycans in the collagen preparations.…”

Section: Racemization Of Aspartic Acid In Human Cartilage Collagen Anmentioning

confidence: 67%

“…There is a close relationship between chronological age and D-aspartic acid accumulation in the white matter of the brain (17), the eye lens (16), dentin (18), and bone (19,20). Furthermore, several studies have shown the age-related accumulation of D-aspartic acid in cartilagenous tissues such as the intervertebral disc (21), rib cartilage (22), and articular cartilage (11,23). Measurement of aspartic acid racemization has proven to be a valuable tool to derive quantitative information on protein residence time, i.e.…”

mentioning

confidence: 99%

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Effect of Collagen Turnover on the Accumulation of Advanced Glycation End Products

Verzijl¹,

DeGroot²,

Thorpe³

et al. 2000

Journal of Biological Chemistry

821

593

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Collagen molecules in articular cartilage have an exceptionally long lifetime, which makes them susceptible to the accumulation of advanced glycation end products (AGEs). In fact, in comparison to other collagen-rich tissues, articular cartilage contains relatively high amounts of the AGE pentosidine. To test the hypothesis that this higher AGE accumulation is primarily the result of the slow turnover of cartilage collagen, AGE levels in cartilage and skin collagen were compared with the degree of racemization of aspartic acid (% D-Asp, a measure of the residence time of a protein). AGE (N ⑀ -(carboxymethyl)lysine, N ⑀ -(carboxyethyl)lysine, and pentosidine) and % D-Asp concentrations increased linearly with age in both cartilage and skin collagen (p < 0.0001). The rate of increase in AGEs was greater in cartilage collagen than in skin collagen (p < 0.0001). % D-Asp was also higher in cartilage collagen than in skin collagen (p < 0.0001), indicating that cartilage collagen has a longer residence time in the tissue, and thus a slower turnover, than skin collagen. In both types of collagen, AGE concentrations increased linearly with % D-Asp (p < 0.0005). Interestingly, the slopes of the curves of AGEs versus % D-Asp, i.e. the rates of accumulation of AGEs corrected for turnover, were identical for cartilage and skin collagen. The present study thus provides the first experimental evidence that protein turnover is a major determinant in AGE accumulation in different collagen types. From the age-related increases in % D-Asp the half-life of cartilage collagen was calculated to be 117 years and that of skin collagen 15 years, thereby providing the first reasonable estimates of the half-lives of these collagens.Nonenzymatic glycation is a post-translational modification of proteins in vivo, which is initiated by the spontaneous reaction of sugars with lysine residues in proteins and eventually results in the formation of advanced glycation end products (AGEs), 1 such as N ⑀ -(carboxymethyl)lysine (CML), N ⑀ -(carboxyethyl)lysine (CEL), and pentosidine (1-3). Because AGEs are irreversible chemical modifications of protein, they accumulate with age in long lived proteins such as lens crystallins and tissue collagens (1, 3-9). Because collagen molecules in articular cartilage have an exceptionally long lifetime (Ͼ100 years) (10, 11), they are highly susceptible to the accumulation of AGEs. Indeed, in comparison to other collagen-rich tissues (such as skin), articular cartilage contains relatively high amounts of pentosidine (3, 12). Although differences in AGE levels between different proteins have been attributed to differences in protein turnover rates (3,(12)(13)(14), no quantitative evidence to support this assumption is available.To compare protein turnover rates, information on the residence time of a protein in tissue can be obtained from the racemization of aspartic acid. Amino acids are incorporated into peptides and proteins as the L-enantiomers. During aging, racemization slowly converts the L-form into a race...

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Section: Racemization Of Aspartic Acid In Human Cartilage Collagen Anmentioning

confidence: 67%

mentioning

confidence: 99%

Effect of Collagen Turnover on the Accumulation of Advanced Glycation End Products

Verzijl¹,

DeGroot²,

Thorpe³

et al. 2000

Journal of Biological Chemistry

821

593

View full text Add to dashboard Cite

show abstract

“…Several sites in the human body, including lung (Shapiro et al 1991), heart (Powell et al 1992), brain (Shapira et al 1988), teeth (Helfman and Bada 1975), skin (Verzijl et al 2000), intervertebral discs (Ritz and Schutz 1993) and cartilage (Maroudas et al 1992) contain abundant proteins that are very long-lived, with half-lives measured in decades.…”

Section: Introductionmentioning

confidence: 99%

Racemisation and human cataract. d-Ser, d-Asp/Asn and d-Thr are higher in the lifelong proteins of cataract lenses than in age-matched normal lenses

Hooi

Truscott

2010

AGE

107

122

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Astract Several amino acids were found to undergo progressive age-dependent racemisation in the lifelong proteins of normal human lenses. The two most highly racemised were Ser and Asx. By age 70, 4.5% of all Ser residues had been racemised, along with >9% of Asx residues. Such a high level of inversion, equivalent to between 2 and 3 D -amino acids per polypeptide chain, is likely to induce significant denaturation of the crystallins in aged lenses. Thr, Glx and Phe underwent age-dependent racemisation to a smaller degree. In model experiments, D -amino acid content could be increased simply by exposing intact lenses to elevated temperature. In cataract lenses, the extent of racemisation of Ser, Asx and Thr residues was significantly greater than for agematched normal lenses. This was true, even for cataract lenses removed from patients at the earliest ages where age-related cataract is observed clinically. Racemisation of amino acids in crystallins may arise due to prolonged exposure of these proteins to ocular temperatures and increased levels of racemisation may play a significant role in the opacification of human lenses.

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“…[49][50][51] Agedependent amino acid racemization also has been observed in proteins found in vertebral discs and the eye lens. [52][53][54][55] In theory, the racemization process is not directly coupled to the aging of the individual, but is simply a process that depends on when proteins were first generated in the body.…”

Section: Chemical and Molecular Biological Methodsmentioning

confidence: 99%

Age estimation of skeletal remains: principal methods

Villa¹,

Lynnerup²

2014

RRFMS

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Abstract:The age of an individual is often a fundamental piece of data in connection with forensic identification of unidentified bodies. The methods most often used are based on visually determining various morphological, age-related changes in the skeleton (or teeth, although odontological methods are not reviewed in this paper). As such, these methods are all relative: ie, they do not obtain results in calendar years but estimates of the age at death, often with a rather large range. Recently, methods have been proposed for more direct ascertainment of age at death: eg, protein racemization and radiocarbon methods. The latter method, especially, may yield absolute age (year of birth), because radiocarbon activity (as measured in specific proteins in specific cells or tissues of the body) may be in equilibrium with the so-called bomb-pulse, when atmospheric radiocarbon content has changed markedly from one year to another. This review covers the basic and most often used gross morphological methods, radiologically-based methods, biochemical methods, and radiocarbon dating.

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Aspartic Acid Racemization in Intervertebral Discs as an Aid to Postmortem Estimation of Age at Death

Cited by 49 publications

References 22 publications

Effect of Collagen Turnover on the Accumulation of Advanced Glycation End Products

Effect of Collagen Turnover on the Accumulation of Advanced Glycation End Products

Racemisation and human cataract. d-Ser, d-Asp/Asn and d-Thr are higher in the lifelong proteins of cataract lenses than in age-matched normal lenses

Age estimation of skeletal remains: principal methods

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