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Inositol Polyphosphate Multikinase (IPMK) a Gene Coding for a Potential Moonlighting Protein Contributes to Human Female Longevity

机译:肌醇多磷酸多激酶(IPMK)一种编码潜在月光蛋白的基因有助于人类女性的长寿

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摘要

Biogerontological research highlighted a complex and dynamic connection between aging, health and longevity, partially determined by genetic factors. Multifunctional proteins with moonlighting features, by integrating different cellular activities in the space and time, may explain part of this complexity. Inositol Polyphosphate Multikinase (IPMK) is a potential moonlighting protein performing multiple unrelated functions. Initially identified as a key enzyme for inositol phosphates synthesis, small messengers regulating many aspects of cell physiology, IPMK is now implicated in a number of metabolic pathways affecting the aging process. IPMK regulates basic transcription, telomere homeostasis, nutrient-sensing, metabolism and oxidative stress. Here, we tested the hypothesis that the genetic variability of IPMK may affect human longevity. Single-SNP (single nuclear polymorphism), haplotype-based association tests as well as survival analysis pointed to the relevance of six out of fourteen genotyped SNPs for female longevity. In particular, haplotype analysis refined the association highlighting two SNPs, rs2790234 and rs6481383, as major contributing variants for longevity in women. Our work, the first to investigate the association between variants of IPMK and longevity, supports IPMK as a novel gender-specific genetic determinant of human longevity, playing a role in the complex network of genetic factors involved in human survival.
机译:生物老年医学研究强调了衰老,健康与长寿之间的复杂而动态的联系,部分原因是遗传因素决定的。通过在时空上整合不同的细胞活动,具有月光功能的多功能蛋白质可以解释这种复杂性的部分原因。肌醇多磷酸多激酶(IPMK)是一种潜在的月光蛋白,具有多种无关的功能。 IPMK最初被确定为肌醇磷酸酯合成的关键酶,是调节细胞生理学许多方面的小信使,现在与许多影响衰老过程的代谢途径有关。 IPMK调节基本转录,端粒稳态,营养感应,新陈代谢和氧化应激。在这里,我们测试了IPMK的遗传变异性可能影响人类寿命的假设。单SNP(单核多态性),基于单倍型的关联测试以及生存分析指出,十四种基因型SNP中有六种与女性寿命相关。特别是,单倍型分析完善了该关联,突出了两个SNP,即rs2790234和rs6481383,它们是女性长寿的主要贡献变体。我们的工作是第一个研究IPMK变异与寿命之间关系的研究,它支持IPMK作为人类寿命的新型性别特异性遗传决定因素,在涉及人类生存的复杂遗传因素网络中发挥作用。

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