Genetic and pharmacological factors that influence reproductive aging in nematodes.
Genetic and pharmacological factors that influence reproductive aging in nematodes.
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DOI：
10.1371/journal.pgen.0030025
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发表时间：
2007-02-16
期刊：
影响因子：
4.5
通讯作者：
Kornfeld K
中科院分区：
文献类型：
--
作者：
Hughes SE;Evason K;Xiong C;Kornfeld K
生殖系统中与年龄相关的退行性变化是衰老的一个重要方面，因为生殖成功是进化适应性的主要决定因素。秀丽隐杆线虫是研究躯体衰老的重要生物体，因为许多延长成年寿命的因素已被确定。然而，控制线虫或其他动物生殖衰老的机制尚不清楚。为了利用秀丽隐杆线虫测量生殖衰老，我们分析了未耗尽精子的交配雌雄同体，并监测了后代产生的持续时间和水平。交配的雌雄同体表现出后代产量的下降，最终导致在寿命结束前生殖停止，这表明雌雄同体经历了生殖衰老。为了确定影响生殖衰老的因素，我们分析了延长寿命的遗传、环境和药理学因素。饮食限制和胰岛素/胰岛素样生长因子信号减少可延迟生殖衰老，表明营养状况和响应环境压力的信号通路会影响生殖衰老。寒冷的气温延缓了生殖衰老。影响神经活动的抗惊厥药物乙舒酰亚胺可以延缓生殖衰老，表明神经活动可以影响生殖衰老。其中一些因素会降低早期后代的产量，但在寿命延长的菌株中，早期后代的产量与生殖衰老之间并没有一致的关系。为了直接检查早期后代生产对生殖衰老的影响，我们利用精子的可用性来调节早期生殖水平。早期后代的产生既不加速也不延迟生殖衰老，表明生殖衰老不受使用依赖机制控制。讨论了这些发现对衰老进化理论的影响。在动物中，衰老的特点是退行性变化，组织和器官的功能逐渐减弱。生命支持系统的退行性变化最终导致死亡，而生殖系统的退行性变化最终导致后代生产的停止。成功的繁殖是动物生命的最终目的，因此确定生殖衰老的原因以及进化过程中自然选择塑造生殖衰老的方式非常重要。由于大多数衰老研究都集中在体细胞退化和寿命上，因此对生殖衰老的原因知之甚少。为了识别和表征影响生殖衰老的因素，我们使用了线虫秀丽隐杆线虫，它是研究躯体衰老的重要模型。我们的研究结果表明，低温、限制营养吸收、减少胰岛素信号以及作用于神经系统的抗惊厥药物可以延缓线虫的生殖衰老。这些研究确定了影响生殖衰老的遗传途径和环境因素。令人惊讶的是，生殖衰老在生殖期早期并不受后代产生的影响，这表明使用生殖系产生后代不会加速退行性变化。这些结果表明，生殖衰老不是由使用依赖机制引起的。
Age-related degenerative changes in the reproductive system are an important aspect of aging, because reproductive success is the major determinant of evolutionary fitness. Caenorhabditis elegans is a prominent organism for studies of somatic aging, since many factors that extend adult lifespan have been identified. However, mechanisms that control reproductive aging in nematodes or other animals are not well characterized. To use C. elegans to measure reproductive aging, we analyzed mated hermaphrodites that do not become sperm depleted and monitored the duration and level of progeny production. Mated hermaphrodites display a decline of progeny production that culminates in reproductive cessation before the end of the lifespan, demonstrating that hermaphrodites undergo reproductive aging. To identify factors that influence reproductive aging, we analyzed genetic, environmental, and pharmacological factors that extend lifespan. Dietary restriction and reduced insulin/insulin-like growth factor signaling delayed reproductive aging, indicating that nutritional status and a signaling pathway that responds to environmental stress influence reproductive aging. Cold temperature delayed reproductive aging. The anticonvulsant medicine ethosuximide, which affects neural activity, delayed reproductive aging, indicating that neural activity can influence reproductive aging. Some of these factors decrease early progeny production, but there is no consistent relationship between early progeny production and reproductive aging in strains with an extended lifespan. To directly examine the effects of early progeny production on reproductive aging, we used sperm availability to modulate the level of early reproduction. Early progeny production neither accelerated nor delayed reproductive aging, indicating that reproductive aging is not controlled by use-dependent mechanisms. The implications of these findings for evolutionary theories of aging are discussed. In animals, aging is characterized by degenerative changes that progressively diminish the function of tissues and organs. Degenerative changes in life support systems eventually cause death, whereas degenerative changes in reproductive systems eventually cause the cessation of progeny production. Successful reproduction is the ultimate purpose of animal life, and therefore it is important to determine the causes of reproductive aging and the way reproductive aging has been sculpted by natural selection during evolution. Because most aging studies focus on somatic degeneration and lifespan, relatively little is known about the causes of reproductive aging. To identify and characterize factors that influence reproductive aging, we used the nematode worm C. elegans, which is a prominent model for studies of somatic aging. Our results indicate that reproductive aging in worms can be delayed by cold temperature, by restricting nutrient uptake, by diminishing insulin signaling, and by an anticonvulsant medicine that acts on the nervous system. These studies identify genetic pathways and environmental factors that influence reproductive aging. Surprisingly, reproductive aging was not influenced by progeny production early in the reproductive period, indicating that using the germ line to produce progeny does not accelerate degenerative changes. These results suggest that reproductive aging is not caused by use-dependent mechanisms.
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DOI：
10.1073/pnas.0400848101
发表时间：
2004-05-25
影响因子：
11.1
作者：
Huang, C;Xiong, CJ;Kornfeld, K
通讯作者：
Kornfeld, K
影响因子：
--
作者：
BALL, ZB;BARNES, RH;VISSCHER, MB
通讯作者：
VISSCHER, MB
影响因子：
4.2
作者：
BERG, BN
通讯作者：
BERG, BN
影响因子：
56.9
作者：
Ewbank, JJ;Barnes, TM;Hekimi, S
通讯作者：
Hekimi, S
影响因子：
64.5
作者：
Apfeld, J;Kenyon, C
通讯作者：
Kenyon, C