Aging-related occurrence in Ashkenazi Jews of leukocyte heteroplasmic mtDNA mutation adjacent to replication origin frequently remodeled in Italian centenarians.
Our previous observation that a mitochondrial DNA (mtDNA) homoplasmic C150T transition adjacent to the heavy strand replication origin at position 151 is greatly increased in frequency in Italian centenarians, as compared to the rest of the population, has prompted us to analyze a genetically distinct population to determine how robust the association of the C150T mutation with longevity is. In particular, we have analyzed leukocyte mtDNA from three groups of an Ashkenazi Jew population, namely, a large number (124) of female centenarians and near-centenarians (95-108 years-old), their mixed gender offspring, and mixed gender control subjects. This analysis revealed a very low incidence of the C150T transition in the probands and the other two groups, and by contrast, the fairly high frequency of a homoplasmic T152C transition and of a homoplasmic T195C transition in all three groups of subjects. Furthermore, most significantly, an aging-related increase in incidence of the heteroplasmic T152C transition, presumably resulting from somatic events, was demonstrated in the Ashkenazi Jews. The T152C transition was not associated with a change in the replication origin at position 151, unlike the C150T transition in the Italian centenarians.
Iwata
Nahoko
N
Division of Biology, 156-29, California Institute of Technology, Pasadena, CA 91125, USA.
Zhang
Jin
J
Atzmon
Gil
G
Leanza
Suzanne
S
Cho
Jaehyoung
J
Chomyn
Anne
A
Burk
Robert D
RD
Barzilai
Nir
N
Attardi
Giuseppe
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D007558:Italy / Q000453:epidemiology; D007585:Jews / Q000235:genetics*; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000453:epidemiology / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D018741:Replication Origin / Q000235:genetics*
D004272:DNA, Mitochondrial