Abstract
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.
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