Effects of ageing on nuclear DNA integrity and metabolism in mussel cells (Mytilus edulis L.) |
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| Affiliation: | 1. Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands;2. Center for Environmental Quality, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands;3. Institute for Environmental Studies (IVM), VU University, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands;4. Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA, USA;5. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA |
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| Abstract: | As the age of a cell increases, so does the potential for DNA damage. Recent theories on ageing suggest accumulative DNA damage is the primary cause of cellular senescence, possibly due to the decreased ability of DNA to act as a template for gene expression.In this paper we investigate the effects of ageing on the level of nuclear DNA damage in tissues of wild mussels of three different age groups; 2–4 years (group I), 6–8 years (group II) and 10 years (group III). In the digestive gland and haemolymph cells, a significant age-dependent increase of DNA damage was observed, as evaluated by the fluorimetric alkaline DNA unwinding technique, which is able to detect both direct single strand DNA breaks as well as alkali-labile apurinic sites.In addition, the rate of DNA polymerase activity was studied in order to determine whether DNA damage was dependent on DNA alteration, or because of a reduced rate of DNA repair. Unscheduled DNA repair synthesis in isolated nuclei of digestive gland cells in older mussels, was significantly decreased in comparison to younger mussels (−42% in group II and −37% in group III, p<0.01). In the digestive gland, salt extraction gives a slight, but significant, decrease of aphidicolin-sensitive DNA polymerase activity in age group III of −25%, p<0.05.Finally, we looked at the age variation in relation to oxidative stress. This was evaluated by measuring malondialdehyde accumulation in mussel cells. Digestive gland cells of group III, showed a significant age-related increase in malondialdehyde content of 170%, p<0.01, indicative of enhanced peroxidative processes.Taken together, these data suggest that the accumulation of DNA damage in group II is mainly dependent on the impairment of DNA repair systems. This is contrary to group III DNA damage, where a possible relationship between oxidative stress and alteration of nuclear DNA metabolism is found, probably deriving from an antioxidant defence decline. |
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