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Strikingly higher frequency in centenarians and twins of mtDNA mutation causing remodeling of replication origin in leukocytes.
https://repo.qst.go.jp/records/43127
https://repo.qst.go.jp/records/431273cab3ef6-004d-4a10-b5fb-ff7d4c6e8a7e
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2003-08-11 | |||||
| タイトル | ||||||
| タイトル | Strikingly higher frequency in centenarians and twins of mtDNA mutation causing remodeling of replication origin in leukocytes. | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Jin, Zhang
× Jin, Zhang× Jordi, Asin-cayuela× Fish, Jennifer× Michikawa, Yuichi× Massimiliano, Bonafe× Fabiola, Olivieri× Giuseppe, Passarino× De.benedictis, Giovanna× Claudio, Franceschi× Attardi, Giuseppe× 道川 祐市 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | The presence of a genetic component in longevity is well known. Here, the association of a mtDNA mutation with a prolonged life span in humans was investigated. Large-scale screening of the mtDNA main control region in leukocytes from subjects of an Italian population revealed a homoplasmic C150T transition near an origin of heavy mtDNA-strand synthesis in approximately 17% of 52 subjects 99-106 years old, but, in contrast, in only 3.4% of 117 younger individuals (P = 0.0035). Evidence was obtained for the contribution of somatic events, under probable nuclear genetic control, to the striking selective accumulation of the mutation in centenarians. In another study, among leukocyte mtDNA samples from 20 monozygotic and 18 dizygotic twins, 60-75 years old, 30% (P = 0.0007) and 22% (P = 0.011), respectively, of the individuals involved exhibited the homoplasmic C150T mutation. In a different system, i.e., in five human fibroblast longitudinal studies, convincing evidence for the aging-related somatic expansion of the C150T mutation, up to homoplasmy, was obtained. Most significantly, 5' end analysis of nascent heavy mtDNA strands consistently revealed a new replication origin at position 149, substituting for that at 151, only in C150T mutation-carrying samples of fibroblasts or immortalized lymphocytes. Considering the aging-related health risks that the centenarians have survived and the developmental risks of twin gestations, it is proposed that selection for a remodeled replication origin, inherited or somatically acquired, provides a survival advantage and underlies the observed high incidence of the C150T mutation in centenarians and twins. | |||||
| 書誌情報 |
Proceedings of the National Academy of Sciences of the United States of America 巻 100, 号 3, p. 1116-1121, 発行日 2003-02 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0027-8424 | |||||
