title: The mitochondrial DNA control region shows genetically correlated levels of heteroplasmy in leukocytes of centenarians and their offspring.
abstract: BACKGROUND
  Studies on heteroplasmy occurring in the mitochondrial DNA (mtDNA) control region (CR) in leukocytes of centenarians and younger subjects have shown that the C150T somatic transition is over-represented in centenarians. However, whether the occurrence/accumulation of heteroplasmy is a phenotypic consequence of extreme ageing or a genetically controlled event that may favor longevity is a question that deserves further attention. To clarify this point, we set up a Denaturing High Performance Liquid Chromatography (DHPLC) protocol to quantify mtDNA CR heteroplasmy. We then analyzed heteroplasmy in leukocytes of centenarians (100 subjects), their offspring and nieces/nephews (200 subjects, age-range 65-80 years, median age 70 years), and in leukocytes of 114 control subjects sex- and age-matched with the relatives of centenarians.
  
  
  RESULTS
  The centenarians and their descendants, despite the different ages, showed similar levels of heteroplasmy which were significantly higher than levels in controls. In addition we found that heteroplasmy levels were significantly correlated in parent-offspring pairs (r = 0.263; p = 0.009), but were independent of mtDNA inherited variability (haplogroup and sequence analyses).
  
  
  CONCLUSIONS
  Our findings suggest that the high degree of heteroplasmy observed in centenarians is genetically controlled, and that such genetic control is independent of mtDNA variability and likely due to the nuclear genome.
authors.affiliation: Department of Cell Biology, University of Calabria, 87036 Rende, Italy. pinarose@unical.it
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Rose
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Passarino
authors.forename: Vittorio
authors.initials: V
authors.lastname: Scornaienchi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Romeo
authors.forename: Serena
authors.initials: S
authors.lastname: Dato
authors.forename: Dina
authors.initials: D
authors.lastname: Bellizzi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mari
authors.forename: Emidio
authors.initials: E
authors.lastname: Feraco
authors.forename: Raffaele
authors.initials: R
authors.lastname: Maletta
authors.forename: Amalia
authors.initials: A
authors.lastname: Bruni
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.forename: Giovanna
authors.initials: G
authors.lastname: De Benedictis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D017931:DNA Primers; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000648:ultrastructure*; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D012680:Sensitivity and Specificity
chemical_list: D017931:DNA Primers; D004272:DNA, Mitochondrial