Somatic mutations accompany humans from beginning to end

The ageing process leads to function loss and more disease susceptibility. Somatic mutations play a major role in neurodegenerative diseases and cancer.

The nine molecular features of ageing

The ageing process of the human organism is characterised by a progressive loss of physiological integrity. This leads to functional limitations as well as an increased susceptibility to death. Neurodegenerative, cardiovascular, metabolic, and oncological diseases may develop as a result. According to scientific studies, the rate of ageing is controlled by evolutionarily determined genetic pathways and biochemical processes.

These include telomere attrition, genomic instability, loss of proteostasis, epigenetic changes, impaired nutrient sensitivity, mitochondrial dysfunction, cell senescence, stem cell depletion, and altered intercellular communication.1,3

Somatic mutations accumulate with age

Dr Campbell presented the allocation theory at this year's EHA 2023 participants. This states that within the human body, different priorities are set after the reproductive age. Maintenance processes compete with fertility and growth processes in the body for the available resources. With regard to the ageing process, Dr Campbell emphasised that there is an accumulation of somatic mutations. He listed a few examples of this:

Over the course of a life, various research groups have observed a linear increase in somatic mutations in the various organ systems of the human body. Even in differentiated or post-mitotic cells such as lymphoid cells or neurons, an increase in mutations with age has been observed.1

Mutations start from the moment of conception

Somatic mutations already occur during fetal development. This was observed by the research group led by Spencer Chapman, of which Dr Campbell was a member. They found that in healthy foetuses, individual haematopoietic progenitors acquired a large number of somatic mutations up to 18 weeks after conception. Dr Campbell and his scientific colleagues hypothesised that the somatic mutation rate during the 2nd-3rd cell division after conception must already be 1-2 mutations.1,4

Driver mutations start from the moment of conception

If somatic mutations lead to a growth advantage of a tumour cell by occurring in crucial areas within signal transduction, these are called driver mutations. They have a proliferation-promoting effect in the appropriate microenvironment and can result in clonal expansion. Campbell highlighted in his presentation that various research groups have observed an increase in driver mutations with advancing age.1

Somatic mutations are a part of human life and accompany humans from beginning to end. Here, the somatic mutation rate correlates with age. The occurrence of driver mutations promotes the proliferation of tumour cells and can result in various oncological disease patterns.1

  1. Campbell, Peter, Dr. med., Special lecture: Somatic mutations in ageing and disease, 28. Jahrestagung der European Hematology Association (EHA) in Frankfurt, 8-15 Juni 2023.
  3. López-Otín C. et al. (2013). The hallmarks of aging. Cell. 2013 Jun 6;153(6):1194-217. 
  4. Spencer Chapman M, Ranzoni AM, Myers B, Williams N, Coorens THH, Mitchell E, Butler T, Dawson KJ, Hooks Y, Moore L, Nangalia J, Robinson PS, Yoshida K, Hook E, Campbell PJ, Cvejic A. Lineage tracing of human development through somatic mutations. Nature. 2021 Jul;595(7865):85-90.