Folate Acts in E. coli to Accelerate C. elegans Aging Independently of Bacterial Biosynthesis.
Folate Acts in E. coli to Accelerate C. elegans Aging Independently of Bacterial Biosynthesis.
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DOI：
10.1016/j.celrep.2016.01.051
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发表时间：
2016-02-23
期刊：
影响因子：
8.8
通讯作者：
Weinkove D
中科院分区：
文献类型：
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作者：
Virk B;Jia J;Maynard CA;Raimundo A;Lefebvre J;Richards SA;Chetina N;Liang Y;Helliwell N;Cipinska M;Weinkove D
叶酸是所有真核和原核细胞中生物合成酶的辅助因子。动物不能合成叶酸，必须从饮食或微生物群中获取叶酸。之前，我们发现抑制大肠杆菌叶酸合成可以延长秀丽隐杆线虫的寿命。在这里，我们表明限制或补充线虫叶酸不会影响寿命。因此，大肠杆菌需要叶酸来缩短蠕虫的寿命。肠道中的细菌增殖被认为是大肠杆菌缩短寿命的一种机制。然而，我们在筛选 1,000 多个大肠杆菌缺失突变体时发现，秀丽隐杆线虫的存活率和细菌生长之间没有相关性。九个突变体显着延长了蠕虫的寿命，这表明大肠杆菌的缩短寿命活动需要特定的基因调控。破坏叶酸生物合成循环并不会延长寿命。因此，叶酸通过大肠杆菌中不依赖生长的途径发挥作用，加速动物衰老。限制大肠杆菌中的叶酸，而不是线虫中的叶酸，可以延长蠕虫寿命 大肠杆菌蠕虫寿命筛选将叶酸合成确定为目标 叶酸合成影响大肠杆菌生理机能，与生长无关 细菌叶酸合成可能是慢性疾病的可持续目标 Virk 等人。研究表明，抑制大肠杆菌叶酸合成并不会通过改变线虫叶酸来延长线虫寿命，而是通过大肠杆菌活性发挥作用。他们发现了九种可以延长寿命的大肠杆菌突变体。基因特性表明，轻微的细菌毒性会加速宿主衰老。
Folates are cofactors for biosynthetic enzymes in all eukaryotic and prokaryotic cells. Animals cannot synthesize folate and must acquire it from their diet or microbiota. Previously, we showed that inhibiting E. coli folate synthesis increases C. elegans lifespan. Here, we show that restriction or supplementation of C. elegans folate does not influence lifespan. Thus, folate is required in E. coli to shorten worm lifespan. Bacterial proliferation in the intestine has been proposed as a mechanism for the life-shortening influence of E. coli. However, we found no correlation between C. elegans survival and bacterial growth in a screen of 1,000+ E. coli deletion mutants. Nine mutants increased worm lifespan robustly, suggesting specific gene regulation is required for the life-shortening activity of E. coli. Disrupting the biosynthetic folate cycle did not increase lifespan. Thus, folate acts through a growth-independent route in E. coli to accelerate animal aging. Limiting folate in E. coli, not in C. elegans, increases worm lifespan An E. coli screen for worm longevity identifies folate synthesis as a target Folate synthesis influences E. coli physiology independently of growth Bacterial folate synthesis may be a sustainable target for chronic disease Virk et al. show that inhibiting E. coli folate synthesis does not increase C. elegans lifespan through changes to C. elegans folate, but by acting through an E. coli activity. They find nine E. coli mutants that extend lifespan. The gene identities suggest that mild bacterial toxicities accelerate host aging.