Choi Haeri, Cho Sung Chun, Ha Young Wan, Ocampo Billie, Park Shirley, Chen Shiwen, Bennett Christopher F, Han Jeehae, Rossner Ryan, Kang Jong-Sun, Lee Yun-Ll, Park Sang Chul, Kaeberlein Matt
Department of Obstetrics & Gynecology, Oregon Health and Science University, Portland, OR 97239 USA.
Center for Developmental Health, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR 97239 USA.
Transl Med Aging. 2019;3:64-69. doi: 10.1016/j.tma.2019.07.001. Epub 2019 Jul 3.
The antibiotic diaminodiphenyl sulfone (DDS) is used in combination with other antibiotics as a first line treatment for leprosy. DDS has been previously reported to extend lifespan in through inhibition of pyruvate kinase and decreased mitochondrial function. Here we report an alternative mechanism of action by which DDS promotes longevity in by reducing folate production by the microbiome. This results in altered methionine cycle metabolite levels mimicking the effects of metformin and lifespan extension that is dependent on the starvation- and hypoxia-induced flavin containing monoxygenase, FMO-2.
抗生素二氨基二苯砜（DDS）与其他抗生素联合使用，作为麻风病的一线治疗药物。此前有报道称，DDS通过抑制丙酮酸激酶和降低线粒体功能来延长线虫的寿命。在此，我们报告了一种替代作用机制，即DDS通过减少微生物群产生的叶酸来促进线虫的长寿。这导致甲硫氨酸循环代谢物水平发生改变，模拟了二甲双胍的作用以及依赖于饥饿和缺氧诱导的含黄素单加氧酶FMO-2的寿命延长。
