Experimentally reduced insulin/IGF‐1 signaling in adulthood extends lifespan of parents and improves Darwinian fitness of their offspring
Abstract 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 repro...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Oxford University Press
2019-04-01
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| Series: | Evolution Letters |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/evl3.108 |
| _version_ | 1797765775752167424 |
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| author | Martin I. Lind Sanjana Ravindran Zuzana Sekajova Hanne Carlsson Andrea Hinas Alexei A. Maklakov |
| author_facet | Martin I. Lind Sanjana Ravindran Zuzana Sekajova Hanne Carlsson Andrea Hinas Alexei A. Maklakov |
| author_sort | Martin I. Lind |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-12T20:14:56Z |
| format | Article |
| id | doaj.art-bf42f6d800d3430fa0da04a46d6a4592 |
| institution | Directory Open Access Journal |
| issn | 2056-3744 |
| language | English |
| last_indexed | 2024-03-12T20:14:56Z |
| publishDate | 2019-04-01 |
| publisher | Oxford University Press |
| record_format | Article |
| series | Evolution Letters |
| spelling | doaj.art-bf42f6d800d3430fa0da04a46d6a45922023-08-02T01:23:52ZengOxford University PressEvolution Letters2056-37442019-04-013220721610.1002/evl3.108Experimentally reduced insulin/IGF‐1 signaling in adulthood extends lifespan of parents and improves Darwinian fitness of their offspringMartin I. Lind0Sanjana Ravindran1Zuzana Sekajova2Hanne Carlsson3Andrea Hinas4Alexei A. Maklakov5Animal Ecology, Department of Ecology and Genetics Uppsala University Uppsala 752 36 SwedenAnimal Ecology, Department of Ecology and Genetics Uppsala University Uppsala 752 36 SwedenAnimal Ecology, Department of Ecology and Genetics Uppsala University Uppsala 752 36 SwedenAnimal Ecology, Department of Ecology and Genetics Uppsala University Uppsala 752 36 SwedenDepartment of Cell and Molecular Biology Uppsala University Uppsala 751 24 SwedenAnimal Ecology, Department of Ecology and Genetics Uppsala University Uppsala 752 36 SwedenAbstract 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.https://doi.org/10.1002/evl3.108Ageingantagonistic pleiotropyfunctional trade‐offshyperfunctionIIS signalingparental effects |
| spellingShingle | Martin I. Lind Sanjana Ravindran Zuzana Sekajova Hanne Carlsson Andrea Hinas Alexei A. Maklakov Experimentally reduced insulin/IGF‐1 signaling in adulthood extends lifespan of parents and improves Darwinian fitness of their offspring Evolution Letters Ageing antagonistic pleiotropy functional trade‐offs hyperfunction IIS signaling parental effects |
| title | Experimentally reduced insulin/IGF‐1 signaling in adulthood extends lifespan of parents and improves Darwinian fitness of their offspring |
| title_full | Experimentally reduced insulin/IGF‐1 signaling in adulthood extends lifespan of parents and improves Darwinian fitness of their offspring |
| title_fullStr | Experimentally reduced insulin/IGF‐1 signaling in adulthood extends lifespan of parents and improves Darwinian fitness of their offspring |
| title_full_unstemmed | Experimentally reduced insulin/IGF‐1 signaling in adulthood extends lifespan of parents and improves Darwinian fitness of their offspring |
| title_short | Experimentally reduced insulin/IGF‐1 signaling in adulthood extends lifespan of parents and improves Darwinian fitness of their offspring |
| title_sort | experimentally reduced insulin igf 1 signaling in adulthood extends lifespan of parents and improves darwinian fitness of their offspring |
| topic | Ageing antagonistic pleiotropy functional trade‐offs hyperfunction IIS signaling parental effects |
| url | https://doi.org/10.1002/evl3.108 |
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