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in the bone marrow
Whole-genome sequencing has revealed hundreds of somatic mutations in healthy white blood cells (WBCs) from a 115-year-old woman, but the mutations appear to be harmless.
The research also suggests that most of the woman’s peripheral WBCs originated from 2 related hematopoietic stem cell (HSC) clones.
And the WBCs had telomeres that were significantly shorter than telomeres from other tissues.
Study investigators said these findings indicate that the finite lifespan of HSCs, rather than the effects of somatic mutations, may lead to hematopoietic clonal evolution at “extreme ages.”
Henne Holstege, PhD, of VU University Medical Center in Amsterdam, The Netherlands, and her colleagues detailed these findings in Genome Research.
The team conducted this study to determine if, over a long lifetime, mutations can accumulate in healthy WBCs. The WBCs were donated by a supercentenarian woman, who, at the time of her death in 2005, was the oldest person in the world.
The investigators performed deep whole-genome sequencing of the woman’s WBCs. And, based on the results, they estimated that about 450 somatic mutations accumulated in the non-repetitive genome within the healthy blood compartment, which suggests that about 600 somatic mutations accumulated in the whole genome of the HSC clone.
The mutations were not tumor-derived, and only a few were detected at minimal frequencies in other tissues. The team did not detect these mutations in the brain, which rarely undergoes cell division after birth.
In addition, the mutations appeared to be tolerated by the body. And they resided primarily in non-coding regions of the genome not previously associated with disease. This included sites that are especially mutation-prone, such as methylated cytosine DNA bases and solvent-accessible stretches of DNA.
Another key finding of this research was that about 65% of the healthy blood compartment was populated by the offspring of 2 HSC clones, and 1 of these was likely derived from the other.
The investigators said a possible explanation for this oligoclonality might be found in the extremely short telomere lengths of the woman’s WBCs. The WBC telomeres were 17 times shorter than telomeres in the brain.
“Because these blood cells had extremely short telomeres, we speculate that most hematopoietic stem cells may have died from stem cell exhaustion, reaching the upper limit of stem cell divisions,” Dr Holstege said.
So the team believes the oligoclonality they observed may be a consequence of HSCs’ finite lifespan. 
in the bone marrow
Whole-genome sequencing has revealed hundreds of somatic mutations in healthy white blood cells (WBCs) from a 115-year-old woman, but the mutations appear to be harmless.
The research also suggests that most of the woman’s peripheral WBCs originated from 2 related hematopoietic stem cell (HSC) clones.
And the WBCs had telomeres that were significantly shorter than telomeres from other tissues.
Study investigators said these findings indicate that the finite lifespan of HSCs, rather than the effects of somatic mutations, may lead to hematopoietic clonal evolution at “extreme ages.”
Henne Holstege, PhD, of VU University Medical Center in Amsterdam, The Netherlands, and her colleagues detailed these findings in Genome Research.
The team conducted this study to determine if, over a long lifetime, mutations can accumulate in healthy WBCs. The WBCs were donated by a supercentenarian woman, who, at the time of her death in 2005, was the oldest person in the world.
The investigators performed deep whole-genome sequencing of the woman’s WBCs. And, based on the results, they estimated that about 450 somatic mutations accumulated in the non-repetitive genome within the healthy blood compartment, which suggests that about 600 somatic mutations accumulated in the whole genome of the HSC clone.
The mutations were not tumor-derived, and only a few were detected at minimal frequencies in other tissues. The team did not detect these mutations in the brain, which rarely undergoes cell division after birth.
In addition, the mutations appeared to be tolerated by the body. And they resided primarily in non-coding regions of the genome not previously associated with disease. This included sites that are especially mutation-prone, such as methylated cytosine DNA bases and solvent-accessible stretches of DNA.
Another key finding of this research was that about 65% of the healthy blood compartment was populated by the offspring of 2 HSC clones, and 1 of these was likely derived from the other.
The investigators said a possible explanation for this oligoclonality might be found in the extremely short telomere lengths of the woman’s WBCs. The WBC telomeres were 17 times shorter than telomeres in the brain.
“Because these blood cells had extremely short telomeres, we speculate that most hematopoietic stem cells may have died from stem cell exhaustion, reaching the upper limit of stem cell divisions,” Dr Holstege said.
So the team believes the oligoclonality they observed may be a consequence of HSCs’ finite lifespan.
in the bone marrow
Whole-genome sequencing has revealed hundreds of somatic mutations in healthy white blood cells (WBCs) from a 115-year-old woman, but the mutations appear to be harmless.
The research also suggests that most of the woman’s peripheral WBCs originated from 2 related hematopoietic stem cell (HSC) clones.
And the WBCs had telomeres that were significantly shorter than telomeres from other tissues.
Study investigators said these findings indicate that the finite lifespan of HSCs, rather than the effects of somatic mutations, may lead to hematopoietic clonal evolution at “extreme ages.”
Henne Holstege, PhD, of VU University Medical Center in Amsterdam, The Netherlands, and her colleagues detailed these findings in Genome Research.
The team conducted this study to determine if, over a long lifetime, mutations can accumulate in healthy WBCs. The WBCs were donated by a supercentenarian woman, who, at the time of her death in 2005, was the oldest person in the world.
The investigators performed deep whole-genome sequencing of the woman’s WBCs. And, based on the results, they estimated that about 450 somatic mutations accumulated in the non-repetitive genome within the healthy blood compartment, which suggests that about 600 somatic mutations accumulated in the whole genome of the HSC clone.
The mutations were not tumor-derived, and only a few were detected at minimal frequencies in other tissues. The team did not detect these mutations in the brain, which rarely undergoes cell division after birth.
In addition, the mutations appeared to be tolerated by the body. And they resided primarily in non-coding regions of the genome not previously associated with disease. This included sites that are especially mutation-prone, such as methylated cytosine DNA bases and solvent-accessible stretches of DNA.
Another key finding of this research was that about 65% of the healthy blood compartment was populated by the offspring of 2 HSC clones, and 1 of these was likely derived from the other.
The investigators said a possible explanation for this oligoclonality might be found in the extremely short telomere lengths of the woman’s WBCs. The WBC telomeres were 17 times shorter than telomeres in the brain.
“Because these blood cells had extremely short telomeres, we speculate that most hematopoietic stem cells may have died from stem cell exhaustion, reaching the upper limit of stem cell divisions,” Dr Holstege said.
So the team believes the oligoclonality they observed may be a consequence of HSCs’ finite lifespan.