Analysis of cancer genomes reveals basic features of human aging and its role in cancer development.
Analysis of cancer genomes reveals basic features of human aging and its role in cancer development.
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DOI：
10.1038/ncomms12157
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发表时间：
2016-08-12
影响因子：
16.6
通讯作者：
Gladyshev VN
中科院分区：
文献类型：
--
作者：
Podolskiy DI;Lobanov AV;Kryukov GV;Gladyshev VN
长期以来，体细胞突变与衰老和疾病有关，但它们对健康和功能的影响很难评估。通过分析人类癌症基因组，我们确定了与衰老相关的突变模式。我们的分析表明，与年龄相关的突变负荷和负担大约每8年翻一番，类似于全因死亡率翻一番的时间。该分析进一步揭示了不同人体组织之间衰老速率的差异，例如，生殖系统的衰老略有加速。基因组调整的突变负荷和负担与相应的癌症发病率相关，平均提前15年，指向临床前癌症发展时间。突变负荷的行为也表现出性别差异和晚年逆转，解释了癌症发病率中的一些性别特异性和晚年模式。总体而言，这项研究描述了人类衰老的一些特征，并提供了年龄成为癌症发病危险因素的机制。 体细胞突变与疾病有关，包括癌症。在这里，作者分析了癌症基因组数据，并表明体细胞突变随着年龄的增长而增加，癌症发病率落后于这种增长15年，在以后的生活中，突变和癌症发病率降低。
Somatic mutations have long been implicated in aging and disease, but their impact on fitness and function is difficult to assess. Here by analysing human cancer genomes we identify mutational patterns associated with aging. Our analyses suggest that age-associated mutation load and burden double approximately every 8 years, similar to the all-cause mortality doubling time. This analysis further reveals variance in the rate of aging among different human tissues, for example, slightly accelerated aging of the reproductive system. Age-adjusted mutation load and burden correlate with the corresponding cancer incidence and precede it on average by 15 years, pointing to pre-clinical cancer development times. Behaviour of mutation load also exhibits gender differences and late-life reversals, explaining some gender-specific and late-life patterns in cancer incidence rates. Overall, this study characterizes some features of human aging and offers a mechanism for age being a risk factor for the onset of cancer. Somatic mutations are associated with disease, including cancer. Here, the authors analyse cancer genomic data and show that somatic mutations increase with age and that cancer incidence lags 15 years behind this increase, later in life, mutation and cancer incidence are reduced.