A key role for neuropeptide y in lifespan extension and cancer suppression via dietary restriction

Takuya Chiba, Yukari Tamashiro, Daeui Park, Tatsuya Kusudo, Ryoko Fujie, Toshimitsu Komatsu, Sang Eun Kim, Seongjoon Park, Hiroko Hayashi, Ryoichi Mori, Hitoshi Yamashita, Hae Young Chung, Isao Shimokawa

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Abstract

Knowledge of genes essential for the life-extending effect of dietary restriction (DR) in mammals is incomplete. In this study, we found that neuropeptide Y (Npy), which mediates physiological adaptations to energy deficits, is an essential link between DR and longevity in mice. The lifespan-prolonging effect of lifelong 30% DR was attenuated in Npy-null mice, as was the effect on the occurrence of spontaneous tumors and oxidative stress responses in comparison to wild-type mice. In contrast, the physiological processes activated during adaptation to DR, including inhibition of anabolic signaling molecules (insulin and insulin-like growth factor-1), modulation of adipokine and corticosterone levels, and preferential fatty acid oxidation, were unaffected by the absence of Npy. These results suggest a key role for Npy in mediating the effects of DR. We also provide evidence that most of the physiological adaptations to DR could be achieved in mice without Npy.

Original languageEnglish
Article number4517
JournalScientific reports
Volume4
DOIs
Publication statusPublished - 2014 Mar 31

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Chiba, T., Tamashiro, Y., Park, D., Kusudo, T., Fujie, R., Komatsu, T., Kim, S. E., Park, S., Hayashi, H., Mori, R., Yamashita, H., Chung, H. Y., & Shimokawa, I. (2014). A key role for neuropeptide y in lifespan extension and cancer suppression via dietary restriction. Scientific reports, 4, [4517]. https://doi.org/10.1038/srep04517