Low level of the mtDNA(4977) deletion in blood of exceptionally old individuals.

Authors:
Nicole von Wurmb-Schwark, Thorsten Schwark, Amke Caliebe, Carolin Drenske, Susanna Nikolaus, Stefan Schreiber, Almut Nebel
Year of publication:
2010
Volume:
131
Issue:
3
Issn:
0047-6374
Journal title abbreviated:
MECH AGEING DEV
Journal title long:
Mechanisms of ageing and development
Impact factor:
2.892
Abstract: 
The common 4977-bp deletion in mitochondrial DNA (dmtDNA(4977)) occurs frequently in tissues of high oxygen demand and low mitotic activity, e.g. brain, heart and skeletal muscle, where it appears to show an age-related accumulation. Although dmtDNA(4977) can also be detected in very low amounts in fast replicating tissues such as blood, it is still unclear whether an age-dependent distribution of dmtDNA(4977) occurs in blood. In view of these uncertainties, we investigated the presence of the mutation and changes in the dmtDNA(4977) level in whole blood samples from 473 individuals who belong to two different age groups, i.e. elderly (aged 61-75 years) and long-lived individuals (LLI, aged 95-109 years). We applied a highly sensitive and reliable duplex-PCR method that allowed relative quantification of dmtDNA(4977). For validation, we additionally performed absolute quantification on a subset of samples using real time-PCR. Our results showed that the proportion of dmtDNA(4977) carriers was very similar in both groups, but that the individual mutational load was on average much lower in the nonagenarians and centenarians than in the elderly. The finding was independent of smoking habits, gender or variation in APOE and FOXO3A but could be caused by other environmental and/or genetic factors.