101 Facts About Ageing #32: How, When and Where Mutations Occur Throughout Life

As Daniel Patrick Moynihan, an American sociologist, politician, and diplomat once said: “Everyone is entitled to his own opinion, but not his own facts”. And we wholeheartedly agree. A shared set of facts is the first step to building a better world with longevity for all. In that spirit, we are creating a series that covers 101 indisputable facts about ageing, health and longevity.

Throughout life, cells acquire random mutations – changes to the genetic code that occur as a result of replication errors or damage. These mutations are passed on to the cell’s progeny when it divides. Just as we study the genetic ancestry of humans to learn how our species migrated and diversified, so it is possible to trace the lineage of individual cells back to the fertilised egg in order to construct a kind of family tree, which helps us understand how the cells in different parts of our body diverged genetically due to mutation.

Cells begin to diverge due to mutation during embryonic development – even the very first division of the fertilised egg may result in mutations. Mutations during the first few embryonic divisions have been observed to occur at a rate of around 2.4 mutations per generation. The resultant cells will then further divide and specialise into tissue cells, passing their mutations on to their progeny and ‘labelling’ many of the cells in those tissues and organs. Because cells in the early embryo mix a lot, cells that exist within the same tissues can still be very distantly related – even some adjacent cells have been observed to share the fertilised egg as their most recent common ancestor.

Throughout life, cells in some tissues continue to divide (mutating in the process) in order to replace those that die. In such self-renewing tissues, it is common to find genetically similar cells that are descended from a recent common ancestor in the form of a tissue-resident stem cell – an unspecialised cell that retains the capacity to produce multiple different cell types through division. In tissues that do not self-renew like brain tissue, cells are less genetically similar with much more distant shared ancestors. The source of new genetic mutations also varies between tissues. For example, a relatively high number of mutations occurring in the cells of the gastrointestinal tract are the result of replication errors, while mutations in the liver are more likely to be the result of exposure to toxic substances.