Some twenty years ago, Massachusetts Institute of Technology biologist Lenny Guarente began studying aging by timing the lifespan of various yeast strains. Finding one mutant strain that lived about 50% longer than the others, Guarente's team searched the mutant's genome to uncover its secret to long life. The investigation singled out a silent information regulator gene called Sir2, which was expressed at a higher-than-normal rate.
Learning just how Sir2 functions to extend life became Guarente's goal. Only after years of confusing results did he and then-postdoc Shin-ichiro Imai, in a dramatic "Aha!" moment, finally figure it out. Sir2 is not an ADP-ribosylating enzyme--an enzyme that adds ADP ribose to a protein, as some studies had suggested and which they had been trying to prove--but rather, it is a histone deacetylase, an enzyme that removes a small part of a protein (an acetyl group) around which DNA is wound. Furthermore, as ...
