Quantitative analysis of age-associated accumulation of mitochondrial DNA with deletion in human hearts.

We have demonstrated that myocardial mitochondrial DNA (mtDNA) with a 7,436 base-pair deletion existed in all subjects that were over 70 years old. Since each mitochondrion has two or three copies of its own DNA, quantitative analysis is required for the evaluation of the role of mtDNA with deletions in the age-related deterioration of cardiac performance. For this purpose, the kinetic polymerase chain reaction (PCR) method developed in our laboratory was used in this investigation to determine myocardial mtDNA with this 7,436 base-pair deletion in human cadavers of various ages. The mtDNA population with this deletion increased exponentially with age [log f (% of deleted mtDNA) = -3.136 + 0.0454 x age, r = 0.95, P less than 0.01)], and was estimated at 3% and 9% in subjects of age 80 and 90, respectively. The deleted portion encodes 7 subunits of the mitochondrial ATP production system, and a population of mtDNA with this deletion over a certain threshold might induce a significant deterioration of cardiac energy metabolism. Cardiac function is known to deteriorate with age, and an increase in the population of mtDNA with deletion is likely to be an important contributing factor to aged heart (presbycardia).