title: Suppression of phosphoinositide 3-kinase prevents cardiac aging in mice.
abstract: BACKGROUND
  Heart failure is a typical age-associated disease. Although age-related changes of heart are likely to predispose aged people to heart failure, little is known about the molecular mechanism of cardiac aging.
  
  
  RESULTS
  We analyzed age-associated changes in murine heart and the manner in which suppression of the p110alpha isoform of phosphoinositide 3-kinase activity modified cardiac aging. Cardiac function declined in old mice associated with the expression of senescence markers. Accumulation of ubiquitinated protein and lipofuscin, as well as comprehensive gene expression profiling, indicated that dysregulation of protein quality control was a characteristic of cardiac aging. Inhibition of phosphoinositide 3-kinase preserved cardiac function and attenuated expression of the senescence markers associated with enhanced autophagy. Suppression of target of rapamycin, a downstream effector of phosphoinositide 3-kinase, also prevented lipofuscin accumulation in the heart.
  
  
  CONCLUSIONS
  Suppression of phosphoinositide 3-kinase prevented many age-associated changes in the heart and preserved cardiac function of aged mice.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Inuzuka
authors.forename: Junji
authors.initials: J
authors.lastname: Okuda
authors.forename: Tsuneaki
authors.initials: T
authors.lastname: Kawashima
authors.forename: Takao
authors.initials: T
authors.lastname: Kato
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Niizuma
authors.forename: Yodo
authors.initials: Y
authors.lastname: Tamaki
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Iwanaga
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Rie
authors.initials: R
authors.lastname: Kosugi
authors.forename: Kayo
authors.initials: K
authors.lastname: Watanabe-Maeda
authors.forename: Yoji
authors.initials: Y
authors.lastname: Machida
authors.forename: Shingo
authors.initials: S
authors.lastname: Tsuji
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Tohru
authors.initials: T
authors.lastname: Izumi
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Shioi
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D058534:Class I Phosphatidylinositol 3-Kinases; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; C484760:PIK3CA protein, human