Longevity of elastin in human intervertebral disc as probed by the racemization of aspartic acid
2012
Sivan, Sarit-Sara | Van El, Benno | Merkher, Yulia | Schmelzer, Christian E.H. | Zuurmond, Anne-Marie | Heinz, Andrea | Wachtel, Ellen | Varga, Peter-Paul | Lazary, Aron | Brayda-Bruno, Marco | Maroudas, Alice
BACKGROUND: Aging and degeneration of human intervertebral disc (IVD) are associated with biochemical changes, including racemization and glycation. These changes can only be counteracted by protein turnover. Little is known about the longevity of IVD elastin in health or disease. Yet, such knowledge is important for a quantitative understanding of tissue synthesis and degradation. METHODS: We have measured the accumulation of d-Asp and pentosidine in IVD elastin. Samples representing a broad range of ages (28–82years) and degeneration grades (1–5) were analyzed. RESULTS: d/l-Asp for elastin increased linearly with age from 3.2% (early 30s) to 14.8% (early 80s) for normal tissue (grades 1–2) and from 1.7% (late 20s) to 6.0% (until the mid 50s) for degenerate tissue (grades 3–5) with accumulation rates of 16.2±3.1×10⁻⁴ and 11.7±3.8×10⁻⁴year⁻¹, respectively; no significant difference was found between these values (p<0.05). Above the mid 50s, a decrease in d-Asp accumulation was recorded in the degenerate tissue. d-Asp accumulation correlated well with pentosidine content for elastin from healthy and degenerate tissues combined. We conclude that IVD elastin is metabolically‐stable and long‐lived in both healthy and degenerate human IVDs, with signs of new synthesis in the latter. The correlation of d‐Asp with pentosidine content suggests that both these agents may be used as markers in the overall aging process of IVD. GENERAL SIGNIFICANCE: Accumulation of modified IVD elastin argues for its longevity and may have a negative impact on its role in disc function. Weak signs of newly synthesized molecules may act to counteract this effect in degenerate tissue.
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