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

Nat Commun. 2019 Jul 17;10(1):3042. doi: 10.1038/s41467-019-10759-z.


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.

Publication types

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

MeSH terms

  • Aging / genetics
  • Aging / immunology
  • Animals
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / immunology
  • Caenorhabditis elegans Proteins / metabolism*
  • Disease Susceptibility / immunology
  • Fertility / genetics
  • Gene Expression Regulation / physiology*
  • Immunity, Innate / genetics*
  • Longevity / genetics*
  • Mitogen-Activated Protein Kinases / genetics
  • Models, Animal
  • Mutation
  • Peptide Elongation Factors / genetics
  • Peptide Elongation Factors / immunology
  • Peptide Elongation Factors / metabolism*
  • Stress, Physiological / genetics
  • Stress, Physiological / immunology*


  • Caenorhabditis elegans Proteins
  • Peptide Elongation Factors
  • Mitogen-Activated Protein Kinases
  • Pmk-1 protein, C elegans
  • TCER-1 protein, C elegans