The p66Shc knockout mice are short lived under natural condition

Aging Cell

Marco Giorgio¹  Alessandra Berry⁵  Ina Berniakovich¹  Inga Poletaeva⁴  Mirella Trinei¹  Massimo Stendardo¹  Kevork Hagopian²  Jon J. Ramsey²  Gino Cortopassi²  Enrica Migliaccio¹  Sarah Nötzli³  Irmgard Amrein³  Hans P. Lipp³  Francesca Cirulli⁵ 

[1] Department of Experimental Oncology, European Institute of Oncology, 20139 Milan, Italy;Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA;Division of Neuroanatomy and Behavior, Institute of Anatomy, University of Zürich, 8057 Zürich, Switzerland;Laboratory of Physiology and Genetics of Behavior, Department of Biology, Lomonossov Moscow State University, 119991 Moscow, Russia;Department of Cell Biology and Neurosciences, Division of Behavioural Neuroscience, Istituto Superiore di Sanità, 00161 Roma, Italy

关键词: aging genes;    environment;    fat;    fertility;    fitness;    survival;   

DOI  :  10.1111/j.1474-9726.2011.00770.x

来源: Wiley

【 摘 要 】

Summary

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.

【 授权许可】

Unknown   
© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland