Molecular Biology of the Cell Laboratory, Ecole Normale Supérieure de Lyon-CNRS-Université de Lyon Claude Bernard, UMR5239, 46, Allee d'Italie, Lyon, Cedex 07 69364, France.
Helmoltz Zentrum Muenchen-Department of Environmental Sciences (DES)-Analytical BioGeoChemistry (BGC), Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
Nat Commun. 2014 Sep 11;5:4879. doi: 10.1038/ncomms5879.
Dietary restriction (DR) increases healthspan and longevity in many species, including primates, but it is often accompanied by impaired reproductive function. Whether signals associated with the reproductive system contribute to or are required for DR effects on lifespan has not been established. Here we show that expression of the cytochrome P450 DAF-9/CYP450 and production of the steroid hormone Δ(7)-dafachronic acid (DA) are increased in C. elegans subjected to DR. DA signalling through the non-canonical nuclear hormone receptor NHR-8/NHR and the nutrient-responsive kinase let-363/mTOR is essential for DR-mediated longevity. Steroid signalling also affects germline plasticity in response to nutrient deprivation and this is required to achieve lifespan extension. These data demonstrate that steroid signalling links germline physiology to lifespan when nutrients are limited, and establish a central role for let-363/mTOR in integrating signals derived from nutrients and steroid hormones.
饮食限制（DR）可增加许多物种（包括灵长类动物）的健康寿命和寿命，但通常伴随着生殖功能受损。与生殖系统相关的信号是否有助于或需要DR 对寿命的影响尚未确定。在这里，我们表明，在受到 DR 的线虫中，细胞色素 P450 DAF-9/CYP450 的表达和类固醇激素 Δ(7)-dafachronic 酸 (DA) 的产生增加。通过非经典核激素受体 NHR-8/NHR 和营养响应激酶 let-363/mTOR 的 DA 信号对于 DR 介导的长寿是必需的。类固醇信号也影响生殖细胞对营养剥夺的可塑性，这是实现寿命延长所必需的。这些数据表明，当营养物质受到限制时，类固醇信号将生殖细胞生理学与寿命联系起来，并确立了 let-363/mTOR 在整合来自营养物质和类固醇激素的信号方面的核心作用。
