An increase in the probability of death has been a defining feature of aging, yet human perinatal mortality starts high and decreases with age. Previous evolutionary models suggested that organismal aging begins after the onset of reproduction. However, we find that mortality and incidence of diseases associated with aging follow a U-shaped curve with the minimum before puberty, whereas quantitative biomarkers of aging, including somatic mutations and DNA methylation, do not, revealing that aging starts early but is masked by early-life mortality. Moreover, our genetic analyses point to the contribution of damaging mutations to early mortality. We propose that mortality patterns are governed, in part, by negative selection against damaging mutations in early life, manifesting after the corresponding genes are first expressed. Deconvolution of mortality patterns suggests that deleterious changes rather than mortality are the defining characteristic of aging and that aging begins in very early life.

中文翻译：

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衰老的生物标志物，死亡率和破坏性突变的模式阐明了衰老的开始和早期死亡的原因。

死亡几率的增加一直是衰老的决定性特征，但是人类围产期死亡率开始很高，并且随着年龄的增长而降低。以前的进化模型表明，生物衰老是在生殖开始后开始的。但是，我们发现，与衰老相关的疾病的死亡率和发病率呈U型曲线，青春期之前最低，而衰老的定量生物标志物（包括体细胞突变和DNA甲基化）却没有，这表明衰老开始得早，但被衰老掩盖了。早期死亡。此外，我们的遗传分析指出破坏性突变对早期死亡率的贡献。我们提出，死亡率模式部分是通过对早期生命中的破坏性突变的负选择来控制的，这种突变是在相应基因首次表达后才表现出来的。