title: The roles of FoxOs in modulation of aging by calorie restriction.
abstract: FoxO activity and modifications, such as its phosphorylation, acetylation, and methylation, may help drive the expression of genes involved in combating oxidative stress by causing the epigenetic modifications, and thus, preserve cellular function during aging and age-related diseases, such as diabetes, cancer, and Alzheimer disease. Insulin signaling has been postulated to influence the aging process by increasing resistance to oxidative stress, and slowing the accumulation of oxidative damage. Some antioxidative effects are mediated by a conserved family of forkhead box transcription factors (FoxOs), which in the absence of insulin signaling freely bind to promoters of antioxidant enzymes, superoxide dismutase, and catalase. On the other hand, calorie restriction (CR) extends the lifespans of several species via the insulin pathway, and extends longevity and healthspan in diverse species via a conserved mechanism. CR enhances adaptive stress responses at the cellular and organism levels and extends lifespan in a FoxO-independent manner. Thus, increased modification of FoxO is modulated via the hyperinsulinemia-induced PI3K/Akt pathway during aging, and CR reverses this process. Accordingly, FoxO plays an important role in maintenance of metabolic homeostasis and removal of oxidative stress in the aging process and in the effect of CR on lifespan.
authors.affiliation: Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, San 30, Jangjun-dong, Gumjung-gu, Busan, 609-735, Korea.
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Min Hi
authors.initials: MH
authors.lastname: Park
authors.forename: Eun Kyeong
authors.initials: EK
authors.lastname: Lee
authors.forename: Yeon Ja
authors.initials: YJ
authors.lastname: Choi
authors.forename: Ki Wung
authors.initials: KW
authors.lastname: Chung
authors.forename: Kyoung Mi
authors.initials: KM
authors.lastname: Moon
authors.forename: Min Jo
authors.initials: MJ
authors.lastname: Kim
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: An
authors.forename: June Whoun
authors.initials: JW
authors.lastname: Park
authors.forename: Nam Deuk
authors.initials: ND
authors.lastname: Kim
authors.forename: Byung Pal
authors.initials: BP
authors.lastname: Yu
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000375:Aging / Q000502:physiology*; D031204:Caloric Restriction; D051858:Forkhead Transcription Factors / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D051858:Forkhead Transcription Factors; D007328:Insulin