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

doi:10.1038/srep04517

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^*

^*Corresponding author for this work

School of Human Sciences

Research output: Contribution to journal › Article › peer-review

29 Citations (Scopus)

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 language	English
Article number	4517
Journal	Scientific reports
Volume	4
DOIs	https://doi.org/10.1038/srep04517
Publication status	Published - 2014 Mar 31

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title = "A key role for neuropeptide y in lifespan extension and cancer suppression via dietary restriction",

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.",

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

note = "Funding Information: We are grateful to the staff at the Laboratory Animal Center for Biomedical Research at the Center for Frontier Life Sciences, Nagasaki University for their animal care and technical assistance. We also thank Yutaka Araki, Yuko Moriyama, and Rieko Tahara for their excellent technical assistance. The study was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (I.S., nos. 19590227; T.C., nos. 24659181 and 25282027), the 2012 Danone Institute of Japan Foundation Research Grant (T.C.), and the JSPS Asian CORE Program (I.S., nos. FY2010-5).",

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AU - Chiba, Takuya

AU - Tamashiro, Yukari

AU - Park, Daeui

AU - Kusudo, Tatsuya

AU - Fujie, Ryoko

AU - Komatsu, Toshimitsu

AU - Kim, Sang Eun

AU - Park, Seongjoon

AU - Hayashi, Hiroko

AU - Mori, Ryoichi

AU - Yamashita, Hitoshi

AU - Chung, Hae Young

AU - Shimokawa, Isao

N1 - Funding Information: We are grateful to the staff at the Laboratory Animal Center for Biomedical Research at the Center for Frontier Life Sciences, Nagasaki University for their animal care and technical assistance. We also thank Yutaka Araki, Yuko Moriyama, and Rieko Tahara for their excellent technical assistance. The study was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (I.S., nos. 19590227; T.C., nos. 24659181 and 25282027), the 2012 Danone Institute of Japan Foundation Research Grant (T.C.), and the JSPS Asian CORE Program (I.S., nos. FY2010-5).

PY - 2014/3/31

Y1 - 2014/3/31

N2 - 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.

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

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