期刊
REJUVENATION RESEARCH
卷 14, 期 3, 页码 283-291出版社
MARY ANN LIEBERT INC
DOI: 10.1089/rej.2010.1114
关键词
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资金
- Italian Ministry of Health
- Italian Ministry of Research and University [FIRB RBIN04X9XE]
- FIRB project ITALBIONET, Rete Italiana di Bioinformatica
Long-living individuals (LLIs) are used to study exceptional longevity. A number of genetic variants have been found associated in LLIs to date, but further identification of variants would improve knowledge on the mechanisms regulating the rate of aging. Therefore, we performed a genome-wide association study on 410 LLIs and 553 young control individuals with a 317K single-nucleotide polymorphism (SNP) chip to identify novel traits associated with aging. Among the top (p < 1 x 10(-4)) SNPs initially identified, we found rs10491334 (CAMKIV) (odds ratio [OR]=0.55; 95% confidence interval [CI] 0.42-0.73; p = 2.88 x 10(-5)), a variant previously reported associated with diastolic blood pressure, associated also in a replication set of 116 LLIs and 160 controls (OR = 0.54; 95% CI 0.32-0.90; p = 9 x 10(-3)). Furthermore, in vitro analysis established that calcium/calmodulin-dependent protein kinase IV (CAMKIV) activates the survival proteins AKT, SIRT1, and FOXO3A, and we found that homozygous carriers of rs10491334 have a significant reduction in CAMKIV expression. This, together with the observed reduction in minor-allele carriers among centenarians, points to a detrimental role for the SNP. In conclusion, prolongevity genes are activated by CAMKIV, the levels of which are influenced by rs10491334, a SNP associated with human longevity.
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