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

Author

Listed:
  • Francis R. G. Amrit

    (University of Pittsburgh School of Medicine; John G. Rangos Sr. Research Center)

  • Nikki Naim

    (University of Pittsburgh School of Medicine; John G. Rangos Sr. Research Center)

  • Ramesh Ratnappan

    (University of Pittsburgh School of Medicine; John G. Rangos Sr. Research Center)

  • Julia Loose

    (University of Pittsburgh School of Medicine; John G. Rangos Sr. Research Center)

  • Carter Mason

    (University of Pittsburgh School of Medicine; John G. Rangos Sr. Research Center)

  • Laura Steenberge

    (University of Pittsburgh School of Medicine; John G. Rangos Sr. Research Center)

  • Brooke T. McClendon

    (University of Pittsburgh School of Medicine)

  • Guoqiang Wang

    (Rutgers, The State University of New York, Nelson Biological Labs)

  • Monica Driscoll

    (Rutgers, The State University of New York, Nelson Biological Labs)

  • Judith L. Yanowitz

    (University of Pittsburgh School of Medicine)

  • Arjumand Ghazi

    (University of Pittsburgh School of Medicine; John G. Rangos Sr. Research Center)

Abstract

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.

Suggested Citation

  • Francis R. G. Amrit & Nikki Naim & Ramesh Ratnappan & Julia Loose & Carter Mason & Laura Steenberge & Brooke T. McClendon & Guoqiang Wang & Monica Driscoll & Judith L. Yanowitz & Arjumand Ghazi, 2019. "The longevity-promoting factor, TCER-1, widely represses stress resistance and innate immunity," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10759-z
    DOI: 10.1038/s41467-019-10759-z
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