RRC ID |
59435
|
著者 |
Amrit FRG, Naim N, Ratnappan R, Loose J, Mason C, Steenberge L, McClendon BT, Wang G, Driscoll M, Yanowitz JL, Ghazi A.
|
タイトル |
The longevity-promoting factor, TCER-1, widely represses stress resistance and innate immunity.
|
ジャーナル |
Nat Commun
|
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.
|
巻・号 |
10(1)
|
ページ |
3042
|
公開日 |
2019-7-17
|
DOI |
10.1038/s41467-019-10759-z
|
PII |
10.1038/s41467-019-10759-z
|
PMID |
31316054
|
PMC |
PMC6637209
|
MeSH |
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*
|
IF |
11.878
|
引用数 |
3
|
リソース情報 |
線虫 |
tm1452 |