These authors contribute equally to the work.
The p66Shc knockout mice are short lived under natural condition
Version of Record online: 28 DEC 2011
© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland
Volume 11, Issue 1, pages 162–168, February 2012
How to Cite
Giorgio, M., Berry, A., Berniakovich, I., Poletaeva, I., Trinei, M., Stendardo, M., Hagopian, K., Ramsey, J. J., Cortopassi, G., Migliaccio, E., Nötzli, S., Amrein, I., Lipp, H. P., Cirulli, F. and Pelicci, P. G. (2012), The p66Shc knockout mice are short lived under natural condition. Aging Cell, 11: 162–168. doi: 10.1111/j.1474-9726.2011.00770.x
- Issue online: 12 JAN 2012
- Version of Record online: 28 DEC 2011
- Accepted manuscript online: 15 NOV 2011 01:25AM EST
- Accepted for publication 6 November 2011
- aging genes;
Deletion of the p66Shc gene results in lean and healthy mice, retards aging, and protects from aging-associated diseases, raising the question of why p66Shc has been selected, and what is its physiological role. We have investigated survival and reproduction of p66Shc−/− 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 p66Shc was strongly counterselected. Laboratory studies revealed that p66Shc−/− mice have defects in fat accumulation, thermoregulation, and reproduction, suggesting that p66Shc 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.