Open AccessThe p66 Shc knockout mice are short lived under natural condition
Author(s) -
Giorgio Marco,
Berry Alessandra,
Berniakovich Ina,
Poletaeva Inga,
Trinei Mirella,
Stendardo Massimo,
Hagopian Kevork,
Ramsey Jon J.,
Cortopassi Gino,
Migliaccio Enrica,
Nötzli Sarah,
Amrein Irmgard,
Lipp Hans P.,
Cirulli Francesca,
Pelicci Pier G.
Publication year - 2012
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2011.00770.x
Subject(s) - biology , reproduction , longevity , knockout mouse , niche , gene , population , thermoregulation , ecology , genetics , environmental health , medicine
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.