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| 2. |
- Renault, Valérie, et al.
(författare)
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Human skeletal muscle satellite cells : aging, oxidative stress and the mitotic clock
- 2002
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Ingår i: Experimental Gerontology. - : Elsevier. - 0531-5565 .- 1873-6815. ; 37:10-11, s. 1229-1236, Article Number: PII S0531-5565(02)00129-8
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Tidskriftsartikel (refereegranskat)abstract
- Normal satellite cell cultures, isolated from human skeletal muscle, have a limited proliferative capacity and inevitably reach replicative senescence. In this study, we have focused on the consequences of a single oxidative stress by hydrogen peroxide (H(2)O(2)) on both proliferative capacity and myogenic characteristics. Treatment with 1mM H(2)O(2) for 30 min causes a small decrease in the viability and lifespan while the number of cells which are able to proliferate, decreases dramatically. This premature arrest of the cells in a non-proliferative state was not due to spontaneous differentiation since there was no increase in the number of myogenin positive cells. This stress did not affect the myogenicity of the cells or their ability to differentiate and fuse to form multinucleated myotubes. In addition, the mitotic clock does not seem to be modified by oxidative stress treatment since the rate of telomere shortening was similar in H(2)O(2)-treated and control cells. This could be the consequence of the high level of oxygen consumption with an even higher level of ROS being produced in skeletal muscle than in other tissues which would be counteracted by an increase in the antioxidant defense system.
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| 3. |
- Ross, Owen A., et al.
(författare)
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Mitochondrial DNA damage in lymphocytes : a role in immunosenescence?
- 2002
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Ingår i: Experimental Gerontology. - : Elsevier. - 0531-5565 .- 1873-6815. ; 37:2-3, s. 329-340
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Tidskriftsartikel (refereegranskat)abstract
- An age-related increase of DNA damage/mutation has been previously reported in human lymphocytes. The high copy number and mutation rate make the mtDNA genome an ideal candidate for assessing damage and to act as a potential biomarker of ageing. In the present study, two assays were developed to evaluate the level of mtDNA4977 and the accumulation of point mutations with age. A competitive polymerase chain reaction (PCR) methodology incorporating three primers was used to detect and quantify the levels of mtDNA4977 and a novel heteroduplex reference strand conformational analysis (RSCA) technique was used to analyse the accumulation of point mutations. The assays were applied to an in vitro model of T cell ageing and ex vivo DNA samples from an elderly cohort of subjects and a younger control group. The mtDNA4977 was detected in all the DNA samples examined but only a very low concentration was observed and no age-related increase or accumulation was observed. No accumulation of point mutations was identified using RSCA within the T cell clones as they were aged or the ex vivo lymphocytes from the elderly cohort. A higher level of variation was observed within the ex vivo DNA samples, verifying the high resolution of RSCA and its ability to identify different mtDNA species, although no correlation with age was observed. The low level of mtDNA damage observed with respect to the ex vivo lymphocyte DNA samples within this study may be due in part to the high turnover of blood cells/mtDNA, which may inhibit the accumulation of genetically abnormal mtDNA that may play a role in immunosenescence. A similar explanation may also apply to the in vitro model of T cell ageing if the vast majority of the cells are replicating rather than entering senescence.
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| 4. |
- Terman, Alexei, 1957-, et al.
(författare)
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Mitochondrial recycling and aging of cardiac myocytes : The role of autophagocytosis
- 2003
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Ingår i: Experimental Gerontology. - 0531-5565 .- 1873-6815. ; 38:8, s. 863-876
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms of mitochondrial alterations in aged post-mitotic cells, including formation of so-called 'giant' mitochondria, are poorly understood. To test whether these large mitochondria might appear due to imperfect autophagic mitochondrial turnover, we inhibited autophagocytosis in cultured neonatal rat cardiac myocytes with 3-methyladenine. This resulted in abnormal accumulation of mitochondria within myocytes, loss of contractility, and reduced survival time in culture. Unlike normal aging, which is associated with slow accumulation of predominantly large defective mitochondria, pharmacological inhibition of autophagy caused only moderate accumulation of large (senescent-like) mitochondria but dramatically enhanced the numbers of small mitochondria, probably reflecting their normally more rapid turnover. Furthermore, the 3-methyladenine-induced accumulation of large mitochondria was irreversible, while small mitochondria gradually decreased in number after withdrawal of the drug. We, therefore, tentatively conclude that large mitochondria selectively accumulate in aging post-mitotic cells because they are poorly autophagocytosed. Mitochondrial enlargement may result from impaired fission, a possibility supported by depressed DNA synthesis in large mitochondria. Nevertheless, enlarged mitochondria retained immunoreactivity for cytochrome c oxidase subunit 1, implying that mitochondrial genes remain active in defective mitochondria. Our findings suggest that imperfect autophagic recycling of these critical organelles may underlie the progressive mitochondrial damage, which characterizes aging post-mitotic cells.
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| 9. |
- Terman, Alexei, et al.
(författare)
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Myocyte aging and mitochondrial turnover
- 2004
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Ingår i: Experimental Gerontology. - : Elsevier BV. - 0531-5565 .- 1873-6815. ; 39:5, s. 701-705
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Forskningsöversikt (refereegranskat)abstract
- Cardiac myocytes, skeletal muscle fibers, and other long-lived postmitotic cells show dramatic age-related alterations that mainly affect mitochondria and the lysosomal compartment. Mitochondria are primary sites of reactive oxygen species formation that causes progressive damage to mitochondrial DNA and proteins in parallel to intralysosomal lipofuscin accumulation. There is amassing evidence that several various mechanisms may contribute to age-related accumulation of damaged mitochondria following initial oxidative injury. Such mechanisms may include clonal expansion of defective mitochondria, decreased propensity of altered mitochondria to become autophagocytosed (due to mitochondrial enlargement or decreased membrane damage associated with weakened respiration), suppressed autophagy because of heavy lipofuscin loading of lysosomes, and decreased efficiency of Lon protease. © 2004 Elsevier Inc. All rights reserved.
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| 10. |
- Terman, Alexei, 1957-, et al.
(författare)
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Myocyte aging and mitochondrial turnover
- 2004
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Ingår i: Experimental Gerontology. - 0531-5565 .- 1873-6815. ; 39, s. 701-705
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Tidskriftsartikel (refereegranskat)
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