The Maillard hypothesis on aging: Time to focus on DNA
The Maillard hypothesis on aging: Time to focus on DNA
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DOI：
10.1111/j.1749-6632.2002.tb02107.x
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发表时间：
2002-01-01
期刊：
影响因子：
--
通讯作者：
Baynes, JW
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文献类型：
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作者：
Baynes, JW
衰老是生命系统中化学和生物之间竞争的结果。慢性、累积的化学修饰损害了整个身体生物分子的结构和功能。具有长寿命的蛋白质作为暴露于化学损伤的累积物，其以晚期糖基化和脂氧化终产物（AGES，ALES）的形式可检测;被活性氧、氯和氮物质修饰的氨基酸;以及脱酰胺和外消旋氨基酸。并非所有这些修饰都是氧化性的，尽管氧化反应是与年龄相关的损伤的重要来源。蛋白质中AGEs和ALE的测量对于评估美拉德反应损伤的速率和程度是有用的，但是对基因组的损伤无疑对生物体的生存能力具有最大的影响。基因组损伤的程度代表了修饰速率与修复速率和保真度之间的平衡。对DNA的损伤不是以修饰的核酸的形式积累，而是作为修复中的化学“沉默”错误-DNA序列中的插入、缺失、取代、转位和倒位，这些错误影响蛋白质的表达和结构。这些突变是随机的，从一个细胞到另一个细胞各不相同，并从一个细胞世代传递到另一个细胞世代。虽然它们不能检测到DNA中的常规分析技术，嘌呤和嘧啶修饰的美拉德反应中间体可能在尿液中检测到，对这些化合物的研究应该提供洞察的作用，美拉德反应的DNA在衰老和疾病。
Aging is the outcome of the contest between chemistry and biology in living systems. Chronic, cumulative chemical modifications compromise the structure and function of biomolecules throughout the body. Proteins with long life spans serve as cumulators of exposure to chemical damage, which is detectable in the form of advanced glycation and lipoxidation end products (AGES, ALES); amino acids modified by reactive oxygen, chlorine, and nitrogen species; and deamidated and racemized amino acids. Not all of these modifications are oxidative in nature, although oxidative reactions are an important source of age-related damage. Measurements of AGEs and ALEs in proteins are useful for assessing the rate and extent of Maillard reaction damage, but It is the damage to the genome that undoubtedly has the greatest effect on the viability of the organism. The extent of genomic damage represents a balance between the rate of modification and the rate and fidelity of repair. Damage to DNA accumulates not in the form of modified nucleic acids, but as chemically "silent" errors in repair-insertions, deletions, substitutions, transpositions, and inversions in DNA sequences that affect the expression and structure of proteins. These mutations are random, vary from cell to cell, and are passed forward from one cell generation to another. Although they are not detectable in DNA by conventional analytical techniques, purines and pyrimidines modified by Maillard reaction intermediates may be detectable in urine, and studies on these compounds should provide insight into the role of Maillard reactions of DNA in aging and disease.