The mitochondrial theory of aging: Insight from transgenic and knockout mouse models

@article{Jang2009TheMT,
  title={The mitochondrial theory of aging: Insight from transgenic and knockout mouse models},
  author={Youngmok C. Jang and Holly van Remmen},
  journal={Experimental Gerontology},
  year={2009},
  volume={44},
  pages={256-260}
}
  • Y. Jang, H. Remmen
  • Published 1 April 2009
  • Biology, Medicine
  • Experimental Gerontology
Regulation of lifespan by the mitochondrial electron transport chain: reactive oxygen species-dependent and reactive oxygen species-independent mechanisms.
TLDR
It is shown how the regulation of longevity is a complex process whereby ROS-dependent and ROS-independent mechanisms interact to determine the maximum lifespan of species and individuals.
Mitochondrial Involvement in Neurodegeneration and Aging
TLDR
A novel p53 transcriptional response after mtDNA damage is discovered that may directly or partially account for the cellular senescence present in these mice later in life.
Age-dependent mitochondrial energy dynamics in the mice heart: Role of superoxide dismutase-2
Idh2 deficiency accelerates renal dysfunction in aged mice.
When a theory of aging ages badly
TLDR
It is reasonable to now consider the MFRTA as refuted and that it is time to use the insight gained by many years of testing this theory to develop new views as to the physiological causes of aging.
Molecular Mechanisms for Age-Associated Mitochondrial Deficiency in Skeletal Muscle
TLDR
Current knowledge about the molecular mechanisms responsible for age-associated mitochondrial deficiency in skeletal muscle are summarized and recent findings on the role of mtDNA repair and mitochondrial biogenesis in maintaining mitochondrial functionality in aged skeletal muscle will be highlighted.
A midlife crisis for the mitochondrial free radical theory of aging
TLDR
Experimental evidence from comparisons between naturally long- or short-lived animal species, from calorie restricted animals, and from genetically modified animals is reviewed to weigh the strength of results supporting the Mitochondrial Free Radical Theory of Aging.
Mitochondrial longevity pathways.
Animal models of mitochondrial DNA transactions in disease and ageing
TLDR
This article considers the expression of variant proteins, or altered expression of factors involved in these processes in powerful model organisms, such as Drosophila melanogaster and the mouse, which have promoted recognition of the broad relevance of oxidative phosphorylation defects resulting from improper maintenance of mtDNA.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 43 REFERENCES
Alterations in mitochondrial function, hydrogen peroxide release and oxidative damage in mouse hind-limb skeletal muscle during aging
The role of mitochondria in aging of skeletal muscle
TLDR
In this review, several topics will be addressed regarding the age-related loss of skeletal muscle redundancy associated with mitochondrial dysfunction, emphasizing hypotheses for underlying mechanisms and some of the cellular mechanisms that can be pointed out as being responsible.
Reduction of age-associated pathology in old mice by overexpression of catalase in mitochondria.
TLDR
It is reported that MCAT expression is associated with reduced malignant nonhematopoietic tumor burden, reduced cardiac lesions, and a trend toward reduced systemic inflammation, and Antioxidant interventions targeting mitochondria may be a viable strategy for prevention or postpone of some age-associated diseases.
Overexpression of Mn superoxide dismutase does not increase life span in mice.
TLDR
The data show that an approximately twofold overexpression of MnSOD throughout life in mice resulted in decreased lipid peroxidation, increased resistance against paraquat-induced oxidative stress, and decreased age-related decline in mitochondrial ATP production.
Brain mitochondrial dysfunction in aging
TLDR
Conditions that increased mice median life span, such as moderate exercise, vitamin E supplementation, caloric restriction, and high spontaneous neurological activity; also improved neurological performance and mitochondrial function in aged brain.
Thioredoxin 2 haploinsufficiency in mice results in impaired mitochondrial function and increased oxidative stress.
Aging in vertebrates, and the effect of caloric restriction: a mitochondrial free radical production–DNA damage mechanism?
  • G. Barja
  • Biology, Medicine
    Biological reviews of the Cambridge Philosophical Society
  • 2004
TLDR
It is suggested that a low rate of mitochondrial ROS generation extends lifespan both in long‐lived and in caloric‐restricted animals by determining the rate of oxidative attack and accumulation of somatic mutations in mitochondrial DNA.
Mitochondrial DNA Mutations, Oxidative Stress, and Apoptosis in Mammalian Aging
TLDR
It is shown that mice expressing a proofreading-deficient version of the mitochondrial DNA polymerase g (POLG) accumulate mt DNA mutations and display features of accelerated aging, suggesting that accumulation of mtDNA mutations that promote apoptosis may be a central mechanism driving mammalian aging.
Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals
  • G. Barja, A. Herrero
  • Biology, Medicine
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2000
TLDR
The results obtained agree with the notion that oxygen radicals of mitochondrial origin oxidatively damage mtDNA in a way related to the aging rate of each species.
Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging.
TLDR
Life-long reduction of MnSOD activity leads to increased levels of oxidative damage to DNA and increased cancer incidence but does not appear to affect aging.
...
1
2
3
4
5
...