Life Extension in Mice Via p66Shc Refuted
There are many years of studies showing that p66Shc deficiency in mice produces resistance to a number of age related conditions, lowered inflammation, and extended life. Here, however, researchers undertake a more rigorous study and rule out life extension. This is a not infrequent event in the genetics of longevity: a result goes unchallenged for the better part of a decade only to be later refuted when more funding arrives due to increased interest.
The signaling molecule p66Shc is often described as a longevity protein. This conclusion is based on a single life span study that used a small number of mice. The purpose of the present studies was to measure life span in a sufficient number of mice to determine if longevity is altered in mice with decreased Shc levels (ShcKO). Studies were completed at UC Davis and the European Institute of Oncology (EIO).At UC Davis, male C57BL/6J wild type and Shc knockout (ShcKO) mice were fed 5% or 40% calorie-restricted (CR) diets. In the 5% CR group, there was no difference in survival curves between genotypes. There was also no difference between genotypes in prevalence of neoplasms or other measures of end-of-life pathology. At 40% calorie restriction group, 70th percentile survival was increased in ShcKO, while there were no differences between genotypes in median or subsequent life span measures.
At EIO, there was no increase in life span in ShcKO male or female mice on C57BL/6J, 129Sv, or hybrid C57BL/6J-129Sv backgrounds. These studies indicate that p66Shc is not a longevity protein. However, additional studies are needed to determine the extent to which Shc proteins may influence the onset and severity of specific age-related diseases.