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- W834364059 abstract "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. In my doctoral thesis presented here, we show that expression of DAF-9/CYP27A1 and production of the steroid hormone ∆7-dafachronic acid (DA) are increased in C. elegans subjected to DR. DA signaling 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 signaling also affects germline plasticity in response to nutrient deprivation and this is required to achieve lifespan extension. Results presented in my thesis demonstrate that steroid signaling is activated by nutrient scarcity and is required for DR effects on lifespan extension through TOR signaling. In the absence of proper steroid signaling, let-363/mTOR levels remain high during starvation and the number of germ cells within the proliferative zone of the germ line is no longer affected by nutrient availability. Interestingly, genetic reduction of germ cells alleviates the requirement for steroid signaling for DR-mediated lifespan extension. Genetically lowering the germ cell count mimics the response of the germ line to DR. These data demonstrate that steroid signaling 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. We speculate that this induces a signal that is usually emitted when nutrients are scarce and the germ line becomes less active. Taken together, this thesis work suggests that, diet-induced lifespan extension is part of a coordinated response that involves reproductive phenotypes." @default.
- W834364059 created "2016-06-24" @default.
- W834364059 creator A5075370102 @default.
- W834364059 date "2014-11-18" @default.
- W834364059 modified "2023-09-23" @default.
- W834364059 title "Molecular links between nutrition, reproduction and aging" @default.
- W834364059 hasPublicationYear "2014" @default.
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