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


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
17 07 2019
Historique:
received: 25 07 2018
accepted: 29 05 2019
entrez: 19 7 2019
pubmed: 19 7 2019
medline: 28 10 2019
Statut: epublish

Résumé

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.

Identifiants

pubmed: 31316054
doi: 10.1038/s41467-019-10759-z
pii: 10.1038/s41467-019-10759-z
pmc: PMC6637209
doi:

Substances chimiques

Caenorhabditis elegans Proteins 0
Peptide Elongation Factors 0
Mitogen-Activated Protein Kinases EC 2.7.11.24
Pmk-1 protein, C elegans EC 2.7.11.24
TCER-1 protein, C elegans EC 3.6.1.-

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3042

Subventions

Organisme : NIA NIH HHS
ID : R01 AG051659
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
ID : R01AG051659
Pays : International

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Auteurs

Francis R G Amrit (FRG)

Departments of Pediatrics, Developmental Biology and Cell Biology and Physiology, University of Pittsburgh School of Medicine; John G. Rangos Sr. Research Center, Room 7129, One Children's Hospital Drive, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA.

Nikki Naim (N)

Departments of Pediatrics, Developmental Biology and Cell Biology and Physiology, University of Pittsburgh School of Medicine; John G. Rangos Sr. Research Center, Room 7129, One Children's Hospital Drive, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA.

Ramesh Ratnappan (R)

Departments of Pediatrics, Developmental Biology and Cell Biology and Physiology, University of Pittsburgh School of Medicine; John G. Rangos Sr. Research Center, Room 7129, One Children's Hospital Drive, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA.

Julia Loose (J)

Departments of Pediatrics, Developmental Biology and Cell Biology and Physiology, University of Pittsburgh School of Medicine; John G. Rangos Sr. Research Center, Room 7129, One Children's Hospital Drive, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA.

Carter Mason (C)

Departments of Pediatrics, Developmental Biology and Cell Biology and Physiology, University of Pittsburgh School of Medicine; John G. Rangos Sr. Research Center, Room 7129, One Children's Hospital Drive, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA.

Laura Steenberge (L)

Departments of Pediatrics, Developmental Biology and Cell Biology and Physiology, University of Pittsburgh School of Medicine; John G. Rangos Sr. Research Center, Room 7129, One Children's Hospital Drive, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA.

Brooke T McClendon (BT)

Magee-Womens Research Institute, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, 204 Craft Avenue, Pittsburgh, PA, 15213, USA.

Guoqiang Wang (G)

Department of Molecular Biology and Biochemistry, Rutgers, The State University of New York, Nelson Biological Labs, Room A232, Piscataway, NJ, 08854, USA.

Monica Driscoll (M)

Department of Molecular Biology and Biochemistry, Rutgers, The State University of New York, Nelson Biological Labs, Room A232, Piscataway, NJ, 08854, USA.

Judith L Yanowitz (JL)

Magee-Womens Research Institute, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, 204 Craft Avenue, Pittsburgh, PA, 15213, USA.

Arjumand Ghazi (A)

Departments of Pediatrics, Developmental Biology and Cell Biology and Physiology, University of Pittsburgh School of Medicine; John G. Rangos Sr. Research Center, Room 7129, One Children's Hospital Drive, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA. Arjumand.Ghazi@chp.edu.

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