The accumulation of non-enzymatic modifications on both DNA and protein molecules under the attack of reactive oxygen species (ROS), is one of the most possible factors responsible for the functional deterioration in aged cells. Direct protein modifications as well as DNA damages may be detectable, in part, by proteome analysis if the gene expression is affected by the damages on DNA. The novel term "proteome", which is a compound of "protein" and "genome", means a whole set of proteins expressed in a tissue or a cell strain to be investigated. Proteomics is a methodology for analyzing proteomes. In proteomics, two-dimensional gel electrophoresis is performed primarily to separate constitutive proteins, followed by mass spectrometry to identify each protein of interest and to determine a possible post-translational modification. Proteomics has offered us an innovative tool for investigating the molecular mechanisms of cellular aging.