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Aging Cell. 2012 Feb;11(1):162-8. doi: 10.1111/j.1474-9726.2011.00770.x. Epub 2011 Dec 28.

The p66Shc knocked out mice are short lived under natural condition.

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Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.


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.

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