The relationship between somatic structural alteration of the genome and healthy ageing

越来越清楚的是，体细胞突变在衰老的组织中稳步增加。然而，这与健康衰老的确切关系尚不清楚，在其他健康组织中引起体细胞突变的分子和细胞机制仍然不清楚。在这里，我们建议调查的累积结构改变（SA）在老化的人类结肠。我们将确定与健康衰老一致的SA谱（例如，可以累积而不导致病理学的SA），并分析SA累积的大小，类型和速率，以揭示支持“健康”人体突变的潜在分子和细胞机制。

It is increasingly clear that somatic mutations accrue steadily in ageing tissues. However, precisely how this relates to healthy ageing is unknown, and the molecular and cellular mechanisms that cause somatic mutation in otherwise healthy tissue remain poorly defined. Here, we propose to investigate the accrual of structural alterations (SAs) in ageing human colon. We will determine the spectrum of SA that is consistent with healthy ageing (e.g. the SAs that can accrue without leading to a pathology), and profile the size, type and rate of SA accrual to reveal the underlying molecular and cellular mechanisms that underpin 'healthy' human somatic mutagenesis.