Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2005 Dec 27;102(52):18769-70.
doi: 10.1073/pnas.0509776102. Epub 2005 Dec 19.

The mitochondrial theory of aging and its relationship to reactive oxygen species damage and somatic mtDNA mutations

Lawrence A Loeb  1 , Douglas C Wallace, George M Martin
Affiliations
Comment

The mitochondrial theory of aging and its relationship to reactive oxygen species damage and somatic mtDNA mutations

Lawrence A Loeb et al. Proc Natl Acad Sci U S A. .
No abstract available

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.
Mitochondrial DNA damage and aging. Multiple factors may impinge on the integrity of mitochondria that lead to loss of cell function, apoptosis, and aging. The classical pathway is indicated with blue arrows; the generation of ROS (superoxide anion, hydrogen peroxide, and hydroxyl radicals), as a by-product of mitochondrial oxidative phosphorylation, results in damage to mitochondrial macromolecules including the mtDNA, the latter leading to deleterious mutations (3). When these factors damage the mitochondrial energy-generating apparatus beyond a functional threshold, proteins are released from the mitochondria that activate the caspase pathway leading to apoptosis, cell death, and aging. The findings of Trifunovic et al. (4) as well as those of Kujoth et al. (2) now demonstrate that the introduction of excessive mutations in the mtDNA (red arrows) via an error-prone Pol-γ can sufficiently impair mitochondrial function as to result in many of the manifestations of aging without causing a further increase in ROS.
See this image and copyright information in PMC

Comment on

References

    1. Trifunovic, A., Wredenberg, A., Falkenberg, M., Spelbrink, J. N., Rovio, A. T., Bruder, C. E., Bohlooly, Y. M., Gidlof, S., Oldfors, A., Wibom, R., et al. (2004) Nature 429, 357–359. - PubMed
    1. Kujoth, G. C., Hiona, A., Pugh, T. D., Someya, S., Panzer, K., Wohlgemuth, S. E., Hofer, T., Seo, A. Y., Sullivan, R., Jobling, W. A., et al. (2005) Science 309, 481–484. - PubMed
    1. Schriner, S. E., Linford, N. J., Martin, G. M., Treuting, P., Ogburn, C. E., Emond, M., Coskun, P. E., Ladiges, W., Wolf, N., Van Remmen, H., et al. (2005) Science 308, 1909–1911. - PubMed
    1. Trifunovic, A., Hansson, A., Wredenberg, A., Rovio, A. T., Dufour, E., Khvorostov, I., Spelbrink, J. N., Wibom, R., Jacobs, H. T. & Larsson, N.-G. (2005) Proc. Natl. Acad. Sci. USA 102, 17993–17998. - PMC - PubMed
    1. Hansen, A. B., Griner, N. B., Anderson, J. P., Kujoth, G. C., Prolla, T. A., Loeb, L. A. & Glick, E. (2005) DNA Repair, in press. - PubMed