Human stem cell aging: do mitochondrial DNA mutations have a causal role?
Article first published online: 28 JAN 2014
© 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Volume 13, Issue 2, pages 201–205, April 2014
How to Cite
Baines, H. L., Turnbull, D. M. and Greaves, L. C. (2014), Human stem cell aging: do mitochondrial DNA mutations have a causal role?. Aging Cell, 13: 201–205. doi: 10.1111/acel.12199
- Issue published online: 11 MAR 2014
- Article first published online: 28 JAN 2014
- Accepted manuscript online: 31 DEC 2013 05:38AM EST
- Manuscript Accepted: 21 DEC 2013
- Wellcome Trust
- mutator mouse;
- stem cells
A decline in the replicative and regenerative capacity of adult stem cell populations is a major contributor to the aging process. Mitochondrial DNA (mtDNA) mutations clonally expand with age in human stem cell compartments including the colon, small intestine, and stomach, and result in respiratory chain deficiency. Studies in a mouse model with high levels of mtDNA mutations due to a defect in the proofreading domain of the mtDNA polymerase γ (mtDNA mutator mice) have established causal relationships between the accumulation of mtDNA point mutations, stem cell dysfunction, and premature aging. These mtDNA mutator mice have also highlighted that the consequences of mtDNA mutations upon stem cells vary depending on the tissue. In this review, we present evidence that these studies in mice are relevant to normal human stem cell aging and we explore different hypotheses to explain the tissue-specific consequences of mtDNA mutations. In addition, we emphasize the need for a comprehensive analysis of mtDNA mutations and their effects on cellular function in different aging human stem cell populations.