Lind Martin I, Ravindran Sanjana, Sekajova Zuzana, Carlsson Hanne, Hinas Andrea, Maklakov Alexei A
Animal Ecology, Department of Ecology and Genetics Uppsala University Uppsala 752 36 Sweden.
School of Biological Sciences University of East Anglia Norwich NR4 7TJ United Kingdom.
Evol Lett. 2019 Mar 4;3(2):207-216. doi: 10.1002/evl3.108. eCollection 2019 Apr.
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 RNA interference (RNAi) fulfils this prediction in nematodes. Long-lived RNAi parents showed normal fecundity as self-fertilizing hermaphrodites and improved late-life reproduction when mated to males. Remarkably, the offspring of 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.
经典理论认为，衰老通过繁殖和生存之间的能量权衡而演变，导致随着年龄增长未修复的细胞损伤积累。相比之下，新出现的理论假定，衰老的演变是由于促进繁殖的基因在生命后期出现有害的功能亢进，导致生命后期生物合成过度。功能亢进理论独特地预测，在成年期优化营养感应分子信号传导可以同时延缓衰老并提高达尔文适应性。在这里，我们表明，通过RNA干扰（RNAi）降低进化上保守的胰岛素/IGF-1营养感应信号传导，在秀丽隐杆线虫中实现了这一预测。寿命长的RNAi亲本作为自体受精的雌雄同体表现出正常的繁殖力，并且在与雄性交配时改善了生命后期的繁殖。值得注意的是，RNAi亲本的后代在三种不同基因型中具有更高的达尔文适应性。因此，成年期营养感应信号传导的降低改善了亲本的寿命和后代的适应性，支持了新出现的观点，即生命后期次优的基因表达是衰老的核心。
