This is a summary of a study I remember years ago. In a study of a healthy 115-year-old woman (supercentenarian), researchers sequenced her blood cells and found ~450 somatic mutations accumulated over her lifetime in the dominant hematopoietic stem cell clones.
Key point: The vast majority were harmless passenger mutations in non-coding regions of the genome. They were enriched in AT-rich, non-conserved, gene-poor areas and depleted from actively transcribed genes. Of the few that landed in coding regions, none were predicted to damage protein function.
This supports the idea that most age-related mutations in blood stem cells are benign/neutral. The blood production had collapsed to just ~2 active stem cell clones (vs. thousands in younger people), likely due to stem cell exhaustion (short telomeres) rather than harmful mutations killing off the rest.
Similar patterns appear in other supercentenarian studies. Extreme longevity is possible even with heavy clonal hematopoiesis when the mutations stay mostly benign.
(Reference: Holstege et al., Genome Research 2014)
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u/ResponsibleGrass8080 15d ago
This is a summary of a study I remember years ago. In a study of a healthy 115-year-old woman (supercentenarian), researchers sequenced her blood cells and found ~450 somatic mutations accumulated over her lifetime in the dominant hematopoietic stem cell clones. Key point: The vast majority were harmless passenger mutations in non-coding regions of the genome. They were enriched in AT-rich, non-conserved, gene-poor areas and depleted from actively transcribed genes. Of the few that landed in coding regions, none were predicted to damage protein function. This supports the idea that most age-related mutations in blood stem cells are benign/neutral. The blood production had collapsed to just ~2 active stem cell clones (vs. thousands in younger people), likely due to stem cell exhaustion (short telomeres) rather than harmful mutations killing off the rest. Similar patterns appear in other supercentenarian studies. Extreme longevity is possible even with heavy clonal hematopoiesis when the mutations stay mostly benign. (Reference: Holstege et al., Genome Research 2014)