Article

Mice and mitochondria

Nature (Impact Factor: 42.35). 06/2004; 429(6990):357-9. DOI: 10.1038/429357a
Source: PubMed

ABSTRACT It can be hard to work out whether particular events are a cause or a correlate of ageing - do mutations in mitochondrial DNA, for instance, speed up the process of growing old? Some clever studies suggest so.

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Available from: George M. Martin, Jul 29, 2015
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    • "Impaired mitochondrial function is a factor which may be responsible for increased ROS production and therefore predispose to oxidative stress and DNA damage in the aged subjects . Indeed, several studies of the mitochondrial respiratory chain function in humans and animals have demonstrated an age-related decrease in respiration and increased production of ROS during aging [227] [228]. Further support for the age-related decline in mitochondrial function is provided by the demonstration that the amount of COX deficient muscle fibers increases in healthy aging humans [229]. "
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    ABSTRACT: DNA damage and DNA repair may mediate several cellular processes, like replication and transcription, mutagenesis and apoptosis and thus may be important factors in the development and pathology of an organism, including cancer. DNA is constantly damaged by reactive oxygen species (ROS) and reactive nitrogen species (RNS) directly and also by products of lipid peroxidation (LPO), which form exocyclic adducts to DNA bases. A wide variety of oxidatively-generated DNA lesions are present in living cells. 8-oxoguanine (8-oxoGua) is one of the best known DNA lesions due to its mutagenic properties. Among LPO-derived DNA base modifications the most intensively studied are ethenoadenine and ethenocytosine, highly miscoding DNA lesions considered as markers of oxidative stress and promutagenic DNA damage. Although at present it is impossible to directly answer the question concerning involvement of oxidatively damaged DNA in cancer etiology, it is likely that oxidatively modified DNA bases may serve as a source of mutations that initiate carcinogenesis and are involved in aging (i.e. they may be causal factors responsible for these processes). To counteract the deleterious effect of oxidatively damaged DNA, all organisms have developed several DNA repair mechanisms. The efficiency of oxidatively damaged DNA repair was frequently found to be decreased in cancer patients. The present work reviews the basis for the biological significance of DNA damage, particularly effects of 8-oxoGua and ethenoadduct occurrence in DNA in the aspect of cancer development, drawing attention to the multiplicity of proteins with repair activities.
    American Journal of Translational Research 01/2010; 2(3):254-84. · 3.23 Impact Factor
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    • "Impaired mitochondrial function is a factor which may be responsible for increased ROS production and therefore predispose to oxidative stress and DNA damage in the aged subjects. Indeed, several studies of the mitochondrial respiratory chain function in humans and animals have demonstrated an age-related decrease in respiration and an increased production of ROS during aging (Takasawa et al., 1993; Martin & Loeb, 2004). Another support for the age-related decline in mitochondrial function is provided by the demonstration that the amount of COX-deficient muscle fibers increases in healthy aging humans (Kopsidas et al., 1998). "
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    ABSTRACT: Aging is a complex process involving morphologic and biochemical changes in single cells and in the whole organism. One of the most popular explanations of how aging occurs at the molecular level is the oxidative stress hypothesis. Oxidative stress leads in many cases to an age-dependent increase in the cellular level of oxidatively modified macromolecules including DNA, and it is this increase which has been linked to various pathological conditions, such as aging, carcinogenesis, neurodegenerative and cardiovascular diseases. It is, however, possible that a number of short-comings associated with gaps in our knowledge may be responsible for the failure to produce definite results when applied to understanding the role of DNA damage in aging and age-related diseases.
    Acta biochimica Polonica 02/2007; 54(1):11-26. · 1.39 Impact Factor
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    • "One of the most dramatic examples is the male Argiope spider, which dies shortly after copulation by a programmed stop of the heartbeat and is then eaten by the female. The programme theory is further supported by mutant variations of Drosophila and rodents that produce longlived progeny (Martin & Loeb, 2004; Trifunovic et al, 2004), as well as by human genetic defects such as Werner's syndrome and other forms of progeria (accelerated ageing). Apoptosis—the programmed and intrinsically released death of cells—is also known as a characteristic and absolutely necessary phenomenon of normal growth and development (Höffeler, 2004; Brenner & Kroemer, 2000). "
    EMBO Reports 08/2005; 6 Spec No:S14-9. DOI:10.1038/sj.embor.7400425 · 7.86 Impact Factor
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