In a new study published in the journal Genome Research, (Cf Exhibit A), scientists have analyzed a super-centenarian’s blood to better understand why she did not contract serious degenerative diseases until a few years before she died at 115 from metastasized abdomen cancer.
“The subject of our study was W115, a woman who lived to the age of 115 and who was regarded as the oldest human being in the world at the time of her death (Holden 2005). At the age of 82, W115 sent a written consent to donate her body to science after death. W115 had no symptoms of hematological illnesses, and autopsy showed that she did not suffer from vascular or dementia- related pathology. She had breast tumor surgery at age 100 and died 15 years later of a gastric tumor that metastasized into her abdomen (den Dunnen et al. 2008). Since W115 never received mutation- inducing chemotherapy, the somatic mutations in the genomes of her tissues are purely a consequence of normal aging”. (Ibid)
The scientists of this study found that in the years before her death, most of van Andel-Schipper’s white blood cells originated from just two stem cells, indicating that most of the blood stem cells she had been born with had been depleted while her her white blood cells had short telomeres (i.e., the protective caps on chromosomes that erode with each cellular division).
“The distribution of variant allele frequencies of these mutations suggests that the majority of the peripheral white blood cells were offspring of two related hematopoietic stem cell (HSC) clones. Moreover, telomere lengths of the WBCs were significantly shorter than telomere lengths from other tissues. Together, this suggests that the finite lifespan of HSCs, rather than somatic mutation effects, may lead to hematopoietic clonal evolution at extreme ages”. (Ibid.) (2)
It has been estimated that the adult human blood compartment is populated by the offspring of approximately 10,000 – 20,000 hematopoietic stem cells (HSCs) (Abkowitz et al. 2002). (1) At any one time, around 1,000 are simultaneously active to replenish blood,” So from thousands of HSCs, Ms van Andel-Schipper’s “aging process” (via the shortening of telomere mechanism) tapered down to two, from which total depletion and death was followed.
ANALYSIS AND CONCLUSION
From the vantage point of advanced longevity, the results of this study supports the theory of stem cell depletion as a consequence of aging, making human lifespans a function of stem cell renewal.
To mitigate this aging process, holistic medicine’s techniques on stem cell activation (See the Center’s workshops) could be combined with injections of youthful stem cells that could be stored during the earlier years. This means that the youthful stem cells that would be injecting in the elderly body would have much longer telomeres than the elderly stem cells. As a consequence, they would divide much more, be more numerous and be therefore in a position to get the blood and its white blood cells back in shape.
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(1) HSCs self-renew about once every 25–50 wks to create two daughter cells equivalent to their parent, and they differentiate to create offspring clones with multipotent progenitor cells that generate the much larger number of diverse blood cells via hematopoiesis (Catlin et al. 2011). Over time, somatic mutations will gradually accumulate within the HSCs, and the genotypes of the HSCs along with their offspring clones will diverge and lead to new clones of varying sizes.
(2). Because somatic mutations often occur during cell division, frequently dividing cell types are more prone to acquire somatic mutations than tissues that rarely divide (Youssoufian and Pyeritz 2002). Consequently, frequently dividing cell types, i.e., epithelial cells, hematopoietic cells, and male germ cells are vulnerable to somatic mutations that may lead to tumor development or other diseases and disorders. Therefore, most studies regarding somatic mutations have been attempts to discover mechanisms leading to cancer and disease (Youssoufian and Pyeritz 2002; Erickson 2010; Hanahan and Weinberg 2011).
Somatic mutations found in the healthy blood compartment of a 115-yr-old woman demonstrate oligoclonal hematopoiesis by Henne Holstege,1,10 Wayne Pfeiffer,2 Daoud Sie,3 Marc Hulsman,4 Thomas J. Nicholas,5 Clarence C. Lee,6 Tristen Ross,6 Jue Lin,7 Mark A. Miller,2 Bauke Ylstra,3 Hanne Meijers-Heijboer,1 Martijn H. Brugman,8 Frank J.T. Staal,8 Gert Holstege,9 Marcel J.T. Reinders,4 Timothy T. Harkins,6 Samuel Levy,5 and Erik A. Sistermans11Department of Clinical Genetics, VU University Medical Center, 1007 MB Amsterdam, The Netherlands; 2San Diego Supercomputer Center, UCSD, La Jolla, California 92093, USA; 3Department of Pathology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands; 4Delft Bioinformatics Laboratory, Delft University of Technology, 2628 CD Delft, The Netherlands; 5Department of Molecular and Experimental Medicine, Scripps Translational Science Institute, San Diego, California 92037, USA; 6Advanced Applications Group, Life Technologies, Beverly, Massachusetts 01915, USA; 7Department of Biochemistry and Biophysics UCSF,San Francisco, California 94143, USA; 8Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; 9Centre for Clinical Research, University of Queensland, Herston, QLD 4006, Australia
The somatic mutation burden in healthy white blood cells (WBCs) is not well known. Based on deep whole-genome sequencing, we estimate that approximately 450 somatic mutations accumulated in the nonrepetitive genome within the healthy blood compartment of a 115-yr-old woman. The detected mutations appear to have been harmless passenger mutations: They were enriched in noncoding, AT-rich regions that are not evolutionarily conserved, and they were depleted for genomic elements where mutations might have favorable or adverse effects on cellular fitness, such as regions with actively transcribed genes. The distribution of variant allele frequencies of these mutations suggests that the majority of the peripheral white blood cells were offspring of two related hematopoietic stem cell (HSC) clones. Moreover, telomere lengths of the WBCs were significantly shorter than telomere lengths from other tissues. Together, this suggests that the finite lifespan of HSCs, rather than somatic mutation effects, may lead to hematopoietic clonal evolution at extreme ages. Source
Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.162131.113. Freely available online through the Genome Research Open Access option.
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