title: The p66Shc knocked out mice are short lived under natural condition.
abstract: Deletion of the p66(Shc) gene results in lean and healthy mice, retards aging, and protects from aging-associated diseases, raising the question of why p66(Shc) has been selected, and what is its physiological role. We have investigated survival and reproduction of p66(Shc)-/- mice in a population living in a large outdoor enclosure for a year, subjected to food competition and exposed to winter temperatures. Under these conditions, deletion of p66(Shc) was strongly counterselected. Laboratory studies revealed that p66(Shc)-/- mice have defects in fat accumulation, thermoregulation, and reproduction, suggesting that p66(Shc) has been evolutionarily selected because of its role in energy metabolism. These findings imply that the health impact of targeting aging genes might depend on the specific energetic niche and caution should be exercised against premature conclusions regarding gene functions that have only been observed in protected laboratory conditions.
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan, Italy. marco.giorgio@ifom-ieo-campus.it
authors.forename: Marco
authors.initials: M
authors.lastname: Giorgio
authors.forename: Alessandra
authors.initials: A
authors.lastname: Berry
authors.forename: Ina
authors.initials: I
authors.lastname: Berniakovich
authors.forename: Inga
authors.initials: I
authors.lastname: Poletaeva
authors.forename: Mirella
authors.initials: M
authors.lastname: Trinei
authors.forename: Massimo
authors.initials: M
authors.lastname: Stendardo
authors.forename: Kevork
authors.initials: K
authors.lastname: Hagopian
authors.forename: Jon J
authors.initials: JJ
authors.lastname: Ramsey
authors.forename: Gino
authors.initials: G
authors.lastname: Cortopassi
authors.forename: Enrica
authors.initials: E
authors.lastname: Migliaccio
authors.forename: Sarah
authors.initials: S
authors.lastname: Nötzli
authors.forename: Irmgard
authors.initials: I
authors.lastname: Amrein
authors.forename: Hans P
authors.initials: HP
authors.lastname: Lipp
authors.forename: Francesca
authors.initials: F
authors.lastname: Cirulli
authors.forename: Pier G
authors.initials: PG
authors.lastname: Pelicci
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D005075:Biological Evolution; D001833:Body Temperature Regulation / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D056084:Genetic Fitness / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D050356:Lipid Metabolism / Q000235:genetics; D008136:Longevity / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012621:Seasons; D055765:Shc Signaling Adaptor Proteins / Q000172:deficiency / Q000235:genetics*; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
chemical_list: D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1