Human Molecular Genetics, 2002, Vol. 11, No. 3 317-324
© 2002 Oxford University Press
The relationship between somatic mtDNA rearrangements, human heart disease and aging
1Institute of Medical Technology, 2Department of Forensic Medicine, University of Tampere and Tampere University Hospital, 33014 Finland and 3Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK
The lifetime accumulation of low-abundance, somatic mtDNA re-arrangements (sublimons) has been proposed as a potential contributor to aging, and also to diseases such as cardiomyopathy or coronary heart disease. Tissue-specific sublimons, varying in abundance by three orders of magnitude between individuals, have recently been observed in myocardium of control subjects. To study the relationship between myocardial sublimon levels and various types of cardiac disease and aging, we applied a semi-quantitative fluorescent PCR assay on cellular DNA extracted from left ventricle in a series of 300 well characterized male victims of sudden death up to age 70 (Helsinki Sudden Death Study). The most prevalent classes of sublimons were present at <0.1 to 91 copies per cell, but their abundance did not correlate with any cardiac disease phenotype. In multiple regression analyses age (ß = 0.43, P < 0.0001) and smoking (ß = 0.25, P = 0.012) were the only independent factors found to correlate with sublimon levels. Thus, sublimons are inferred to accumulate with age in myocardium of a subset of individuals, but to levels where they do not appear to have any phenotypic effects during a typical life span. We propose that, instead of being a causal factor in cardiac aging, sublimons co-exist with wild-type mtDNA in an equilibrium which is regulated by as yet unknown mechanisms.
+ To whom correspondence should be addressed at: Institute of Medical Technology, University of Tampere, 33014 Finland. Tel: +358 3 215 7731; Fax: +358 3 215 7710; Email: howy.jacobs@uta.fi
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