An antagonistic pleiotropic gene regulates the reproduction and longevity tradeoff

被引：9
作者：
Wu, Dou [1 ,2 ,3 ,4 ]
Wang, Zi [1 ,5 ,6 ,7 ,8 ]
Huang, Jingying [2 ,3 ,4 ]
Huang, Liang [1 ,9 ]
Zhang, Songbo [1 ]
Zhao, Ruixue [2 ,3 ,4 ]
Li, Wei
Chen, Di [5 ,6 ,7 ,8 ]
Ou, Guangshuo [1 ,2 ,3 ,4 ]
机构：
[1] Tsinghua Univ, Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China
[2] Tsinghua Univ, Beijing Frontier Res Ctr Biol Struct, Beijing 100084, Peoples R China
[3] Tsinghua Univ, McGovern Inst Brain Res, Beijing 100084, Peoples R China
[4] Tsinghua Univ, Sch Life Sci, Key Lab Prot Sci, Minist Educ, Beijing 100084, Peoples R China
[5] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210089, Peoples R China
[6] Nanjing Univ, Key Lab Model Anim Dis Study, Minist Educ, Nanjing 210089, Peoples R China
[7] Nanjing Univ, Model Anim Res Ctr, Nanjing 210089, Peoples R China
[8] Nanjing Univ, Inst Brain Sci, Nanjing 210089, Peoples R China
[9] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2022年 / 119卷 / 18期
基金：
中国国家自然科学基金;
关键词：
antagonistic pleiotropy; reproduction; longevity; liquid-liquid phase separation; LIFE-SPAN; INSULIN-RECEPTOR; LIPOPROTEIN; SENESCENCE;
D O I：
10.1073/pnas.2120311119
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
The antagonistic pleiotropy theory of aging proposes that genes enhancing fitness in early life limit the lifespan, but the molecular evidence remains underexplored. By pro-filing translatome changes in Caenorhabditis elegans during starvation recovery, we find that an open reading frame (ORF) trl-1 "hidden" within an annotated pseudogene sig-nificantly translates upon refeeding. trl-1 mutant animals increase brood sizes but shorten the lifespan and specifically impair germline deficiency-induced longevity. The loss of trl-1 abnormally up-regulates the translation of vitellogenin that produces copi-ous yolk to provision eggs, whereas vitellogenin overexpression is known to reduce the lifespan. We show that the TRL-1 protein undergoes liquid-liquid phase separation (LLPS), through which TRL-1 granules recruit vitellogenin messenger RNA and inhibit its translation. These results indicate that trl-1 functions as an antagonistic pleiotropic gene to regulate the reproduction-longevity tradeoff by optimizing nutrient production for the next generation.
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页数：10
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