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端粒酶基因(hTERT)与生存:来自瑞典两个老年人群队列的结果

Telomerase Gene (hTERT) and Survival: Results From Two Swedish Cohorts of Older Adults.

作者信息

Kalpouzos Grégoria, Rizzuto Debora, Keller Lina, Fastbom Johan, Santoni Giola, Angleman Sara, Graff Caroline, Bäckman Lars, Fratiglioni Laura

机构信息

Aging Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet and Stockholm University, Stockholm, Sweden.

Aging Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet and Stockholm University, Stockholm, Sweden. Division of Neurogeriatrics, NVS, Karolinska Institutet, Center for Alzheimer Research at Karolinska Institutet, Stockholm, Sweden.

出版信息

J Gerontol A Biol Sci Med Sci. 2016 Feb;71(2):188-95. doi: 10.1093/gerona/glu222. Epub 2014 Nov 30.

Abstract

Telomere length has been associated with longevity. As telomere length is partly determined by the human telomerase reverse transcriptase (hTERT), we investigated the association between an hTERT polymorphism located in its promoter region ((-) (1327)T/C) and longevity in two cohorts of older adults. Participants from the Kungsholmen project (KP; n = 1,205) and the Swedish National study of Aging and Care in Kungsholmen (SNAC-K; n = 2,764) were followed for an average period of 7.5 years. The main outcomes were hazard ratios (HR) of mortality and median age at death. In both cohorts, mortality was lower in female T/T carriers, aged 75+ years in KP (HR = 0.8, 95% CI: 0.5-0.9) and 78+ years in SNAC-K (HR = 0.6, 95% CI: 0.4-0.8) compared with female C/C carriers. T/T carriers died 1.8-3 years later than the C/C carriers. This effect was not present in men, neither in SNAC-K women aged 60-72 years. The association was not modified by presence of cancer, cardiovascular diseases, number of chronic diseases, or markers of inflammation, and did not interact with APOE genotype or estrogen replacement therapy. The gender-specific increased survival in T/T carriers can be due to a synergistic effect between genetic background and the life-long exposure to endogenous estrogen.

摘要

端粒长度与长寿有关。由于端粒长度部分由人类端粒酶逆转录酶(hTERT)决定,我们在两组老年人群体中研究了位于其启动子区域的hTERT多态性((-)(1327)T/C)与长寿之间的关联。对来自孔斯霍尔门项目(KP;n = 1205)和瑞典孔斯霍尔门衰老与护理国家研究(SNAC-K;n = 2764)的参与者进行了平均7.5年的随访。主要结局是死亡率的风险比(HR)和死亡时的中位年龄。在两个队列中,与女性C/C携带者相比,KP队列中75岁及以上的女性T/T携带者死亡率较低(HR = 0.8,95%CI:0.5 - 0.9),SNAC-K队列中78岁及以上的女性T/T携带者死亡率较低(HR = 0.6,95%CI:0.4 - 0.8)。T/T携带者比C/C携带者晚1.8 - 3年死亡。这种效应在男性中不存在,在SNAC-K队列中60 - 72岁的女性中也不存在。该关联不受癌症、心血管疾病、慢性病数量或炎症标志物的影响,也不与APOE基因型或雌激素替代疗法相互作用。T/T携带者中特定性别的生存增加可能是由于遗传背景与终身内源性雌激素暴露之间的协同作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd47/4707686/715b2e139d8e/gerona_glu222_f0001.jpg

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