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首页> 外文期刊>The journals of gerontology.Series A. Biological sciences and medical sciences >The IRS2 Gly1057Asp variant is associated with human longevity.
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The IRS2 Gly1057Asp variant is associated with human longevity.

机译：IRS2 Gly1057Asp变体与人类寿命有关。

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BACKGROUND: Reduced insulin and insulin-like growth factor-1 (IGF-1) signaling extends the life span of invertebrate and mammals. Recently, reduced insulin receptor substrate-2 (IRS2) signaling was found associated with increased longevity in mice. The aim of our study was to evaluate whether a common polymorphism (Gly1057Asp) in human IRS2 gene is associated with human longevity. METHODS: Six hundred seventy-seven participants (289 males and 388 females) between 16 and 104 years of age, categorized as long lived (LL; >85 years old) or controls (C; <85 years old), were genotyped for Gly1057Asp-IRS2 locus variability (rs1805097). All participants, contacted at home or in their institution or selected from Italian geriatric and internal medicine or geriatric rehabilitation structures, underwent to a clinical, biochemical, and functional characterization, with particular attention to the insulin and IGF-1 signaling. Insulin resistance (Homeostasis Model Assessment [HOMA]-IR), insulin sensitivity (HOMA IS), and ss-cell function (HOMA-B cell) were calculated by the HOMA2 calculator v2.2 (www.dtu.ox.ac.uk/homa). RESULTS: In the whole population, homozygous IRS2(Asp/Asp) participants were more represented among LL versus C participants (16.7% vs 12.0%; p = .04). The association between IRS2 gene polymorphism with longevity (being LL) was independent of anthropometric and metabolic covariates (odds ratio: 2.07, 95% confidence interval [CI] = 1.38-3.12; p = .001). Categorizing participants into percentiles by age, IRS2(Asp/Asp) participants were more likely to reach extreme old age (>or=90 percentile, 96-104 years; odds ratio: 2.03, 95% CI = 1.39-2.99; p = .0003). CONCLUSIONS: These results support the hypothesis that the IRS2 branch of the insulin and IGF signaling is associated with human longevity. Further studies will be necessary for replicating our finding in an independent larger population group with sufficient power before the association between IRS2 gene polymorphism and longevity can be regarded as proven. Furthermore, studies of genetic and/or environmental background interactions may be useful after basic replication is complete.
机译：背景：减少的胰岛素和类胰岛素生长因子-1（IGF-1）信号传导延长了无脊椎动物和哺乳动物的寿命。最近，发现减少的胰岛素受体底物2（IRS2）信号传导与小鼠寿命增加有关。我们研究的目的是评估人类IRS2基因中常见的多态性（Gly1057Asp）是否与人类寿命有关。方法：对167-104岁年龄段的167名参与者（男289例，女388例）进行了Gly1057Asp基因分型，其分类为长寿（LL;> 85岁）或对照组（C; <85岁）。 -IRS2基因座变异性（rs1805097）。在家中或在其机构中联系的所有参与者，或从意大利老年医学和内科医学或老年康复机构中选择的所有参与者均经过临床，生化和功能表征，尤其是胰岛素和IGF-1信号传导。通过HOMA2计算器v2.2（www.dtu.ox.ac.uk）计算了胰岛素抵抗性（稳态模型评估[HOMA] -IR），胰岛素敏感性（HOMA IS）和ss细胞功能（HOMA-B细胞）。 / homa）。结果：在整个人群中，纯合IRS2（Asp / Asp）参与者在LL和C参与者中的比例更高（分别为16.7％和12.0％; p = .04）。 IRS2基因多态性与寿命（LL）之间的关联与人体测量和代谢协变量无关（赔率：2.07，95％置信区间[CI] = 1.38-3.12; p = .001）。按照年龄将参与者分类为百分位，IRS2（Asp / Asp）参与者更有可能达到极端老年（>或= 90％，96-104岁;优势比：2.03，95％CI = 1.39-2.99; p =。 0003）。结论：这些结果支持以下假设：胰岛素的IRS2分支和IGF信号传导与人类寿命有关。在认为IRS2基因多态性和寿命之间存在关联之前，有必要进行进一步的研究以在一个独立的较大人群中以足够的能力复制我们的发现。此外，基本复制完成后，对遗传和/或环境背景相互作用的研究可能会有用。

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