TY - JOUR
T1 - Aging-related occurrence in Ashkenazi Jews of leukocyte heteroplasmic mtDNA mutation adjacent to replication origin frequently remodeled in Italian centenarians
AU - Iwata, Nahoko
AU - Zhang, Jin
AU - Atzmon, Gil
AU - Leanza, Suzanne
AU - Cho, Jaehyoung
AU - Chomyn, Anne
AU - Burk, Robert D.
AU - Barzilai, Nir
AU - Attardi, Giuseppe
N1 - Funding Information:
We thank the subjects for participating in this study. We are grateful to Nicola Raule for valuable discussions and technical advice. This work was supported by the National Institute on Aging (National Institutes of Health) Grant AG12117 and the Ellison Medical Foundation Senior Scholar Award AG-SS-0622-00 (to G.A.), by the Ellison Medical Foundation Senior Scholar Award (AG-18728-01A1) and the General Clinical Research Center (M01-RR12248) at the Albert Einstein College of Medicine (to N. Barzilai and G. Atzmon), and by the Albert Einstein Cancer Center (to R.D. Burk).
PY - 2007/7
Y1 - 2007/7
N2 - 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.
AB - 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.
KW - Longevity
KW - Primer extension
KW - Replication origins
KW - mtDNA replication
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U2 - 10.1016/j.mito.2007.03.001
DO - 10.1016/j.mito.2007.03.001
M3 - Article
C2 - 17452024
AN - SCOPUS:34249050431
SN - 1567-7249
VL - 7
SP - 267
EP - 272
JO - Mitochondrion
JF - Mitochondrion
IS - 4
ER -