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首页> 外文期刊>The journals of gerontology.Series A. Biological sciences and medical sciences >Genetic Regulation of Female Sexual Maturation and Longevity Through Circulating IGF1
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Genetic Regulation of Female Sexual Maturation and Longevity Through Circulating IGF1

机译：通过循环IGF1的女性性成熟和长寿的遗传调控。

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We previously reported that insulin-like growth factor 1 (IGF1) was involved in coregulating female sexual maturation and longevity. To understand the underlying genetic mechanisms, based on the strain survey assays of development and aging traits, we crossed two mouse strains, KK/HIJ and PL/J, and produced 307 female F2 mice. We observed the age of vaginal patency (AVP) and the life span of these females. We also measured circulating IGF1 level at 7, 16, 24, 52, and 76 weeks. IGF1 level at 7 weeks significantly correlated with AVP. IGF1 levels at ages of 52 and 76 weeks negatively correlated with longevity (p <=.05). A gene mapping study found 22, 4, and 3 quantitative trait loci for IGF1, AVP, and life span, respectively. Importantly, the colocalization of IGF1, AVP, and life span quantitative trait loci in the distal region of chromosome 2 suggests this locus carries gene(s) that could regulate IGF1, AVP, and life span. In this region, proprotein convertase subtilisin/kexin type 2 has been found to be associated with female sexual maturation in a human genome-wide association study. We verified the roles of proprotein convertase subtilisin/kexin type 2 in regulating IGF1 and AVP by showing that depletion of proprotein convertase subtilisin/kexin type 2 significantly reduced IGF1 and delayed AVP in mice, suggesting that it also might be involved in the regulation of aging.
机译：我们先前曾报道胰岛素样生长因子1（IGF1）参与调节女性性成熟和长寿。为了了解潜在的遗传机制，基于发育和衰老特征的品系调查分析，我们杂交了两种小鼠品系KK / HIJ和PL / J，并生产了307只雌性F2小鼠。我们观察了这些女性的阴道通畅（AVP）年龄和寿命。我们还测量了7、16、24、52和76周时的循环IGF1水平。 7周时IGF1水平与AVP显着相关。 52和76周龄的IGF1水平与寿命呈负相关（p <=。05）。一项基因作图研究发现了分别为IGF1，AVP和寿命的22、4和3个数量性状基因座。重要的是，IGF1，AVP和寿命量化特征基因座在2号染色体远端区域的共定位表明，该基因座带有可调节IGF1，AVP和寿命的基因。在该区域，在全人类基因组关联研究中，发现前蛋白转化酶枯草杆菌蛋白酶/ kexin 2型与女性性成熟有关。我们通过证明消耗蛋白前体转化酶枯草杆菌蛋白酶/ kexin 2型在小鼠中的IGF1减少和IGP1的减少显着降低了IGF1和AVP的作用，从而证实了它也可能参与了衰老的调控。 。

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