Somatic point mutations in mtDNA control region are influenced by genetic background and associated with healthy aging: a GEHA study

Tissue specific somatic mutations occurring in the mtDNA control region have been proposed to provide a survivaladvantage. Data on twins and on relatives of long-lived subjects suggested that the occurrence/accumulation of thesemutations may be genetically influenced. To further investigate control region somatic heteroplasmy in the elderly, weanalyzed the segment surrounding the nt 150 position (previously reported as specific of Leukocytes) in various types ofleukocytes obtained from 195 ultra-nonagenarians sib-pairs of Italian or Finnish origin collected in the frame of the GEHAProject. We found a significant correlation of the mtDNA control region heteroplasmy between sibs, confirming a geneticinfluence on this phenomenon. Furthermore, many subjects showed heteroplasmy due to mutations different from theC150T transition. In these cases heteroplasmy was correlated within sibpairs in Finnish and northern Italian samples, but notin southern Italians. This suggested that the genetic contribution to control region mutations may be population specific.Finally, we observed a possible correlation between heteroplasmy and Hand Grip strength, one of the best markers ofphysical performance and of mortality risk in the elderly. Our study provides new evidence on the relevance of mtDNAsomatic mutations in aging and longevity and confirms that the occurrence of specific point mutations in the mtDNAcontrol region may represent a strategy for the age-related remodelling of organismal functions.