Activation of Sir2-family proteins in response to calorie restriction (CR) has been proposed as an evolutionarily conserved mechanism for life span extension. This idea has been called into question with the discovery that Sir2-family proteins are not required for life span extension from CR in yeast. We present here a historical perspective and critical evaluation of the model that CR acts through Sir2 in yeast, and interpret prior reports in light of more recent discoveries. Several specific cases where the Sir2 model of CR is inconsistent with experimental data are noted. These shortcomings must be considered along with evidence supporting a role for Sir2 in CR in order to fully evaluate the validity of this model.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Reference||Annotation Extension|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Conditions||Strain||Source||Reference|