Experimentally reduced insulin/IGF-1 signaling in adulthood extends lifespan of parents and improves Darwinian fitness of their offspring

被引:29
作者
Lind, Martin, I [1 ]
Ravindran, Sanjana [1 ]
Sekajova, Zuzana [1 ]
Carlsson, Hanne [1 ,2 ]
Hinas, Andrea [3 ]
Maklakov, Alexei A. [1 ,2 ]
机构
[1] Uppsala Univ, Dept Ecol & Genet, Anim Ecol, S-75236 Uppsala, Sweden
[2] Univ East Anglia, Sch Biol Sci, Norwich NR4 7TJ, Norfolk, England
[3] Uppsala Univ, Dept Cell & Mol Biol, S-75124 Uppsala, Sweden
基金
欧洲研究理事会; 瑞典研究理事会;
关键词
Ageing; antagonistic pleiotropy; functional trade-offs; hyperfunction; IIS signaling; parental effects; senescence; NATURAL-POPULATIONS; SENESCENCE; EVOLUTION; LONGEVITY; MUTATION; SEX; REPRODUCTION; MAINTENANCE; MECHANISMS; SELECTION;
D O I
10.1002/evl3.108
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Classical theory maintains that ageing evolves via energy trade-offs between reproduction and survival leading to accumulation of unrepaired cellular damage with age. In contrast, the emerging new theory postulates that ageing evolves because of deleterious late-life hyper-function of reproduction-promoting genes leading to excessive biosynthesis in late-life. The hyper-function theory uniquely predicts that optimizing nutrient-sensing molecular signaling in adulthood can simultaneously postpone ageing and increase Darwinian fitness. Here, we show that reducing evolutionarily conserved insulin/IGF-1 nutrient-sensing signaling via daf-2 RNA interference (RNAi) fulfils this prediction in Caenorhabditis elegans nematodes. Long-lived daf-2 RNAi parents showed normal fecundity as self-fertilizing hermaphrodites and improved late-life reproduction when mated to males. Remarkably, the offspring of daf-2 RNAi parents had higher Darwinian fitness across three different genotypes. Thus, reduced nutrient-sensing signaling in adulthood improves both parental longevity and offspring fitness supporting the emerging view that suboptimal gene expression in late-life lies at the heart of ageing.
引用
收藏
页码:207 / 216
页数:10
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