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.
authors.affiliation: 1] Department of Investigative Pathology, Unit of Basic Medical Science, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan [2] Department of Pathology, Nagasaki University School of Medicine, Nagasaki 852-8523, Japan [3].
authors.forename: Takuya
authors.initials: T
authors.lastname: Chiba
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine, Nagasaki 852-8523, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Tamashiro
authors.affiliation: Department of Pharmacy, College of Pharmacy, and Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Korea.
authors.forename: Daeui
authors.initials: D
authors.lastname: Park
authors.affiliation: Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai 487-8501, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kusudo
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine, Nagasaki 852-8523, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Fujie
authors.affiliation: 1] Department of Investigative Pathology, Unit of Basic Medical Science, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan [2] Department of Pathology, Nagasaki University School of Medicine, Nagasaki 852-8523, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Komatsu
authors.affiliation: 1] Department of Investigative Pathology, Unit of Basic Medical Science, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan [2] Department of Pathology, Nagasaki University School of Medicine, Nagasaki 852-8523, Japan.
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Kim
authors.affiliation: 1] Department of Investigative Pathology, Unit of Basic Medical Science, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan [2] Department of Pathology, Nagasaki University School of Medicine, Nagasaki 852-8523, Japan.
authors.forename: Seongjoon
authors.initials: S
authors.lastname: Park
authors.affiliation: 1] Department of Investigative Pathology, Unit of Basic Medical Science, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan [2] Department of Pathology, Nagasaki University School of Medicine, Nagasaki 852-8523, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: 1] Department of Investigative Pathology, Unit of Basic Medical Science, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan [2] Department of Pathology, Nagasaki University School of Medicine, Nagasaki 852-8523, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Mori
authors.affiliation: Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai 487-8501, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yamashita
authors.affiliation: Department of Pharmacy, College of Pharmacy, and Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Korea.
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
authors.affiliation: 1] Department of Investigative Pathology, Unit of Basic Medical Science, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan [2] Department of Pathology, Nagasaki University School of Medicine, Nagasaki 852-8523, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Shimokawa
mesh_terms: D000818:Animals; D031204:Caloric Restriction / Q000379:methods; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008136:Longevity / Q000502:physiology*; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009478:Neuropeptide Y / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology
chemical_list: D005227:Fatty Acids; D007328:Insulin; D009478:Neuropeptide Y; D007334:Insulin-Like Growth Factor I