Department of Biology, Ecology and Earth Sciences, University of Calabria, Rende, Italy.
MRC Laboratory for Molecular Cell Biology, University College London, London, UK.
Genes (Basel). 2019 Feb 8;10(2):125. doi: 10.3390/genes10020125.
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 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 and longevity, supports as a novel gender-specific genetic determinant of human longevity, playing a role in the complex network of genetic factors involved in human survival.
生物衰老学研究强调了衰老、健康和长寿之间复杂而动态的联系，部分由遗传因素决定。具有多功能和兼职特性的蛋白质通过在时空上整合不同的细胞活动，可以解释这种复杂性的一部分。肌醇多磷酸激酶（IPMK）是一种具有多种不相关功能的潜在兼职蛋白。最初被鉴定为肌醇磷酸盐合成的关键酶，作为调节细胞生理学许多方面的小分子信使，IPMK 现在与影响衰老过程的许多代谢途径有关。IPMK 调节基本转录、端粒稳态、营养感应、代谢和氧化应激。在这里，我们检验了假设，即 的遗传变异可能影响人类的长寿。单核苷酸多态性（单核苷酸多态性）、基于单倍型的关联测试以及生存分析表明，在 14 个被检测的 SNP 中，有 6 个与女性长寿有关。特别是，单倍型分析对关联进行了细化，突出了 rs2790234 和 rs6481383 这两个 SNP 是女性长寿的主要贡献变体。我们的工作是首次研究 与长寿之间的关联，支持 作为一个新的性别特异性人类长寿遗传决定因素，在涉及人类生存的遗传因素复杂网络中发挥作用。
