The p66 Shc knocked out mice are short lived under natural condition

Marco Giorgio, Alessandra Berry, Ina Berniakovich, Inga Poletaeva, Mirella Trinei, Massimo Stendardo, Kevork Hagopian, Jon J. Ramsey, Gino Cortopassi, Enrica Migliaccio, Sarah Nötzli, Irmgard Amrein, Hans P. Lipp, Francesca Cirulli, Pier G. Pelicci

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)162-168
Number of pages7
JournalAging Cell
Issue number1
Publication statusPublished - Feb 2012


  • Aging genes
  • Environment
  • Fat
  • Fertility
  • Fitness
  • Survival

ASJC Scopus subject areas

  • Cell Biology
  • Ageing


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