title: p66Shc aging protein in control of fibroblasts cell fate.
abstract: Reactive oxygen species (ROS) are wieldy accepted as one of the main factors of the aging process. These highly reactive compounds modify nucleic acids, proteins and lipids and affect the functionality of mitochondria in the first case and ultimately of the cell. Any agent or genetic modification that affects ROS production and detoxification can be expected to influence longevity. On the other hand, genetic manipulations leading to increased longevity can be expected to involve cellular changes that affect ROS metabolism. The 66-kDa isoform of the growth factor adaptor Shc (p66Shc) has been recognized as a relevant factor to the oxygen radical theory of aging. The most recent data indicate that p66Shc protein regulates life span in mammals and its phosphorylation on serine 36 is important for the initiation of cell death upon oxidative stress. Moreover, there is strong evidence that apart from aging, p66Shc may be implicated in many oxidative stress-associated pathologies, such as diabetes, mitochondrial and neurodegenerative disorders and tumorigenesis. This article summarizes recent knowledge about the role of p66Shc in aging and senescence and how this protein can influence ROS production and detoxification, focusing on studies performed on skin and skin fibroblasts.
authors.affiliation: Department of Biochemistry, Nencki Institute of Experimental Biology, Warsaw 02-093, Poland; E-Mails:  j.suski@nencki.gov.pl  (J.M.S.);  mlebiedz@nencki.gov.pl  (M.L.);  j.szczepanowska@nencki.gov.pl  (J.S.);  jdus@nencki.gov.pl  (J.D.).
authors.forename: Jan M
authors.initials: JM
authors.lastname: Suski
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Karkucinska-Wieckowska
authors.forename: Magdalena
authors.initials: M
authors.lastname: Lebiedzinska
authors.forename: Carlotta
authors.initials: C
authors.lastname: Giorgi
authors.forename: Joanna
authors.initials: J
authors.lastname: Szczepanowska
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Szabadkai
authors.forename: Jerzy
authors.initials: J
authors.lastname: Duszynski
authors.forename: Maciej
authors.initials: M
authors.lastname: Pronicki
authors.forename: Paolo
authors.initials: P
authors.lastname: Pinton
authors.forename: Mariusz R
authors.initials: MR
authors.lastname: Wieckowski
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D016922:Cellular Senescence / Q000235:genetics; D004579:Electron Transport; D005347:Fibroblasts / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D008136:Longevity; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D055765:Shc Signaling Adaptor Proteins; D002118:Calcium