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Nat Commun ; 10(1): 3042, 2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31316054

RESUMO

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.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Regulação da Expressão Gênica/fisiologia , Imunidade Inata/genética , Longevidade/genética , Fatores de Alongamento de Peptídeos/metabolismo , Estresse Fisiológico/imunologia , Envelhecimento/genética , Envelhecimento/imunologia , Animais , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/imunologia , Suscetibilidade a Doenças/imunologia , Fertilidade/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Modelos Animais , Mutação , Fatores de Alongamento de Peptídeos/genética , Fatores de Alongamento de Peptídeos/imunologia , Estresse Fisiológico/genética
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