Gene knockout of p66(Shc) is one of the many genetic alterations shown to extend mouse life span. The role of p66(Shc) in the intersection of aging and metabolism has been investigated for more than two decades now, though its ability to extend life is disputed by at least some researchers – the data isn’t as reliable as is the case for some other approaches. This is a common issue for methods that alter the operation of metabolism, as metabolism is very complex, and all sorts of other factors beyond the intended genetic adjustment might have a meaningful influence.
To the extent that p66(Shc) knockout improves health and function in mice, it appears to work via an improvement in mitochondrial activity, or a slowing in the age-related mitochondrial dysfunction that affects unmodified mice. Mitochondria in older individuals produce more oxidative molecules, are less efficient at their primary task of producing chemical energy stores, and their appearance changes, all of which is slowed in p66(Shc) knockout mice. Which is interesting, but what do we get out of this at the end of the day? The papers produced as a result of research into p66(Shc) this year