Accumulating mitochondrial DNA mutations drive premature hematopoietic aging phenotypes distinct from physiological stem cell aging.
(2011) In Cell Stem Cell 8(5). p.499-510- Abstract
- Somatic stem cells mediate tissue maintenance for the lifetime of an organism. Despite the well-established longevity that is a prerequisite for such function, accumulating data argue for compromised stem cell function with age. Identifying the mechanisms underlying age-dependent stem cell dysfunction is therefore key to understanding the aging process. Here, using a model carrying a proofreading-defective mitochondrial DNA polymerase, we demonstrate hematopoietic defects reminiscent of premature HSC aging, including anemia, lymphopenia, and myeloid lineage skewing. However, in contrast to physiological stem cell aging, rapidly accumulating mitochondrial DNA mutations had little functional effect on the hematopoietic stem cell pool, and... (More)
- Somatic stem cells mediate tissue maintenance for the lifetime of an organism. Despite the well-established longevity that is a prerequisite for such function, accumulating data argue for compromised stem cell function with age. Identifying the mechanisms underlying age-dependent stem cell dysfunction is therefore key to understanding the aging process. Here, using a model carrying a proofreading-defective mitochondrial DNA polymerase, we demonstrate hematopoietic defects reminiscent of premature HSC aging, including anemia, lymphopenia, and myeloid lineage skewing. However, in contrast to physiological stem cell aging, rapidly accumulating mitochondrial DNA mutations had little functional effect on the hematopoietic stem cell pool, and instead caused distinct differentiation blocks and/or disappearance of downstream progenitors. These results show that intact mitochondrial function is required for appropriate multilineage stem cell differentiation, but argue against mitochondrial DNA mutations per se being a primary driver of somatic stem cell aging. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1973088
- author
- Norddahl, Gudmundur LU ; Pronk, Kees-Jan LU ; Wahlestedt, Martin LU ; Sten, Gerd LU ; Nygren, Jens LU ; Ugale, Amol LU ; Sigvardsson, Mikael LU and Bryder, David LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cell Stem Cell
- volume
- 8
- issue
- 5
- pages
- 499 - 510
- publisher
- Cell Press
- external identifiers
-
- wos:000290927600011
- pmid:21549326
- scopus:79955698235
- pmid:21549326
- ISSN
- 1934-5909
- DOI
- 10.1016/j.stem.2011.03.009
- language
- English
- LU publication?
- yes
- id
- 72695e5a-7cbc-4d2b-9308-9373051b5167 (old id 1973088)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21549326?dopt=Abstract
- date added to LUP
- 2016-04-04 07:45:55
- date last changed
- 2024-02-27 17:16:33
@article{72695e5a-7cbc-4d2b-9308-9373051b5167, abstract = {{Somatic stem cells mediate tissue maintenance for the lifetime of an organism. Despite the well-established longevity that is a prerequisite for such function, accumulating data argue for compromised stem cell function with age. Identifying the mechanisms underlying age-dependent stem cell dysfunction is therefore key to understanding the aging process. Here, using a model carrying a proofreading-defective mitochondrial DNA polymerase, we demonstrate hematopoietic defects reminiscent of premature HSC aging, including anemia, lymphopenia, and myeloid lineage skewing. However, in contrast to physiological stem cell aging, rapidly accumulating mitochondrial DNA mutations had little functional effect on the hematopoietic stem cell pool, and instead caused distinct differentiation blocks and/or disappearance of downstream progenitors. These results show that intact mitochondrial function is required for appropriate multilineage stem cell differentiation, but argue against mitochondrial DNA mutations per se being a primary driver of somatic stem cell aging.}}, author = {{Norddahl, Gudmundur and Pronk, Kees-Jan and Wahlestedt, Martin and Sten, Gerd and Nygren, Jens and Ugale, Amol and Sigvardsson, Mikael and Bryder, David}}, issn = {{1934-5909}}, language = {{eng}}, number = {{5}}, pages = {{499--510}}, publisher = {{Cell Press}}, series = {{Cell Stem Cell}}, title = {{Accumulating mitochondrial DNA mutations drive premature hematopoietic aging phenotypes distinct from physiological stem cell aging.}}, url = {{http://dx.doi.org/10.1016/j.stem.2011.03.009}}, doi = {{10.1016/j.stem.2011.03.009}}, volume = {{8}}, year = {{2011}}, }