Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism.
Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism.
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DOI：
10.1016/j.cell.2013.02.035
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发表时间：
2013-03-28
期刊：
影响因子：
64.5
通讯作者：
Gems D
中科院分区：
文献类型：
--
作者：
Cabreiro F;Au C;Leung KY;Vergara-Irigaray N;Cochemé HM;Noori T;Weinkove D;Schuster E;Greene ND;Gems D
BIGUANIDE药物二甲双胍被广泛处方以治疗2型糖尿病和代谢综合征，但其作用方式仍然不确定。这会影响健康和衰老。通过蠕虫蛋白合酶（METR-1）和S-腺苷甲硫代合酶（SAMS-1）突变二甲双胍诱导的寿命的改变，这意味着乙蛋白诱导的蛋氨酸在宿主中限制，这与该药物的作用一致根据大肠杆菌菌株的敏感性和葡萄糖浓度增加或降低蠕虫的寿命。疾病。二甲双胍引起的微生物代谢改变可能有助于治疗效果，还导致其副作用，包括叶酸缺乏和胃肠道不适。
►抗糖尿病药物二甲双胍可破坏细菌叶酸和甲基酸酯周期►秀丽隐杆线虫微生物群的这种影响通过甲基二酮限制增加了寿命►二甲双胍仅在存在微生物群的情况下增加寿命，否则是有毒的，并且微生物群可能对乳腺癌介导哺乳动物的健康和粘膜健康和敏捷性健康和敏捷性疗法
二甲双胍被广泛处方用于治疗糖尿病，通过破坏微生物叶酸和蛋白质周期来改变宿主 - 微生物群的寿命，从而诱导蠕虫的方法限制，从而增加寿命。
The biguanide drug metformin is widely prescribed to treat type 2 diabetes and metabolic syndrome, but its mode of action remains uncertain. Metformin also increases lifespan in Caenorhabditis elegans cocultured with Escherichia coli. This bacterium exerts complex nutritional and pathogenic effects on its nematode predator/host that impact health and aging. We report that metformin increases lifespan by altering microbial folate and methionine metabolism. Alterations in metformin-induced longevity by mutation of worm methionine synthase (metr-1) and S-adenosylmethionine synthase (sams-1) imply metformin-induced methionine restriction in the host, consistent with action of this drug as a dietary restriction mimetic. Metformin increases or decreases worm lifespan, depending on E. coli strain metformin sensitivity and glucose concentration. In mammals, the intestinal microbiome influences host metabolism, including development of metabolic disease. Thus, metformin-induced alteration of microbial metabolism could contribute to therapeutic efficacy—and also to its side effects, which include folate deficiency and gastrointestinal upset. ► The antidiabetic drug metformin disrupts bacterial folate and methionine cycles ► This effect in C. elegans microbiota increases lifespan via methionine restriction ► Metformin increases lifespan only if microbiota are present and is otherwise toxic ► Microbiota may mediate metformin effects on mammalian health and aging Metformin, widely prescribed to treat diabetes, induces longevity in worms by altering host-microbiota interactions. By disrupting microbial folate and methionine cycles, metformin induces methionine restriction in the worm, which increases lifespan.
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影响因子：
--
作者：
Hawley SA;Boudeau J;Reid JL;Mustard KJ;Udd L;Mäkelä TP;Alessi DR;Hardie DG
通讯作者：
Hardie DG
影响因子：
7.8
作者：
Kaeberlein, Tammi L.;Smith, Erica D.;Kaeberlein, Matt
通讯作者：
Kaeberlein, Matt
DOI：
10.18632/aging.100273
发表时间：
2011-02
期刊：
Aging
影响因子：
--
作者：
Anisimov VN;Berstein LM;Popovich IG;Zabezhinski MA;Egormin PA;Piskunova TS;Semenchenko AV;Tyndyk ML;Yurova MN;Kovalenko IG;Poroshina TE
通讯作者：
Poroshina TE
影响因子：
56.9
作者：
Garsin, DA;Villanueva, JM;Ausubel, FM
通讯作者：
Ausubel, FM
影响因子：
11.8
作者：
Hannich, J. Thomas;Entchev, Eugeni V.;Kurzchalia, Teymuras V.
通讯作者：
Kurzchalia, Teymuras V.