PT - JOURNAL ARTICLE ED - , TI - Long-Lived Mice Lacking p66<sup>shc</sup> AID - 10.1126/stke.1999.9.tw6 DP - 1999 Nov 23 TA - Science's STKE PG - tw6--tw6 VI - 1999 IP - 9 4099 - http://stke.sciencemag.org/content/1999/9/tw6.short 4100 - http://stke.sciencemag.org/content/1999/9/tw6.full SO - Sci. STKE1999 Nov 23; 1999 AB - As some try to build a better mousetrap, others try to make mice that live longer. The latest advance in the latter category emerges from studies of a signaling protein, p66shc. Although related to p52shc and p46shc proteins that couple receptor tyrosine kinases to activation of Ras, the p66 splice variant seems to signal in a different way. It is phosphorylated on serine residues in response to oxidative stress. Thus it is thought to function in regulation of the response to oxidative damage. What is surprising, though, is that mice that lack p66shc live almost one-third longer than their counterparts that produce the protein. It is not exactly known how this works, but one favored hypothesis is that the p66shc pathway promotes apoptosis in cells that have suffered oxidative damage. Although this strategy may be useful during development, in the aging adult such a pathway might be hazardous to the health. Migliaccio, E., Giorgio, M., Mele, S., Pelicci, G., Reboldi, P., Pandolfi, P.P., Lanfrancone, L., and Pelicci, P.G. (1999) The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature 402: 309-313. [Online Journal]