The longevity-promoting factor, TCER-1, widely represses stress resistance and innate immunity

被引：25

作者：

Amrit, Francis R. G. ^{[1
,2
,3
,4
]}

NairrD, Nikki ^{[1
,2
,3
,4
]}

Ratnappan, Ramesh ^{[1
,2
,3
,4
]}

Loose, Julia ^{[1
,2
,3
,4
]}

Mason, Carter ^{[1
,2
,3
,4
]}

Steenberge, Laura ^{[1
,2
,3
,4
]}

McClendon, Brooke T. ^{[5
]}

Wang, Guoqiang ^{[6
]}

Driscoll, Monica ^{[6
]}

Yanowitz, Judith L. ^{[5
]}

Ghazi, Arjumand ^{[1
,2
,3
,4
]}

机构：

[1] Univ Pittsburgh, Sch Med, Dept Pediat, Room 7129,One Childrens Hosp Dr,4401 Penn Ave, Pittsburgh, PA 15224 USA

[2] Univ Pittsburgh, Sch Med, Dept Dev Biol, Room 7129,One Childrens Hosp Dr,4401 Penn Ave, Pittsburgh, PA 15224 USA

[3] Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Room 7129,One Childrens Hosp Dr,4401 Penn Ave, Pittsburgh, PA 15224 USA

[4] John G Rangos Sr Res Ctr, Room 7129,One Childrens Hosp Dr,4401 Penn Ave, Pittsburgh, PA 15224 USA

[5] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Magee Womens Res Inst, 204 Craft Ave, Pittsburgh, PA 15213 USA

[6] Rutgers State Univ New York, Dept Mol Biol & Biochem, Nelson Biol Labs, Room A232, Piscataway, NJ 08854 USA

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

美国国家卫生研究院;

关键词：

CAENORHABDITIS-ELEGANS; LIFE-SPAN; TRANSCRIPTION FACTOR; SIGNALING PATHWAY; EXPRESSION; INSULIN; AGE; MITOCHONDRIA; PROTEOSTASIS; REPRODUCTION;

D O I：

10.1038/s41467-019-10759-z

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Stress resistance and longevity are positively correlated but emerging evidence indicates that they are physiologically distinct. Identifying factors with distinctive roles in these processes is challenging because pro-longevity genes often enhance stress resistance. We demonstrate that TCER-1, the Caenorhabditis elegans homolog of human transcription elongation and splicing factor, TCERG1, has opposite effects on lifespan and stress resistance. We previously showed that tcer-1 promotes longevity in germline-less C. elegans and reproductive fitness in wild-type animals. Surprisingly, tcer-1 mutants exhibit exceptional resistance against multiple stressors, including infection by human opportunistic pathogens, whereas, TCER-1 overexpression confers immuno-susceptibility. TCER-1 inhibits immunity only during fertile stages of life. Elevating its levels ameliorates the fertility loss caused by infection, suggesting that TCER-1 represses immunity to augment fecundity. TCER-1 acts through repression of PMK-1 as well as PMK-1-independent factors critical for innate immunity. Our data establish key roles for TCER-1 in coordinating immunity, longevity and fertility, and reveal mechanisms that distinguish length of life from functional aspects of aging.

引用

页数：16

共 82 条

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