Besides epigenetic factors, the genetic make-up and differential gene expression not only determines aging and disease susceptibility but also the functional activity of cells in an individual. Analysis of a variety of mammalian tissues revealed that the age-associated differentially expressed genes mainly belong to inflammation, stress, and metabolism. Intracellular PPi is a by-product of multiple biosynthetic reactions and its hydrolysis by cytosolic inorganic pyrophosphatase (iPPase) has long been considered as an important homeostatic mechanism favoring biosynthesis. In this paper we report an age-associated increase (∼2-fold) in the expression of rat liver cytosolic iPPase gene by differential display PCR and northern blot analysis. Expression profiling of iPPase by RNA slot blot analysis in several other tissues revealed no significant change with aging. A comparative spectrophotometric and in-gel analysis of iPPase activity in whole cell lysate (WCL) of liver, brain, skeletal muscle, heart, spleen and kidney exhibited that liver of old rats (24 months ) has ∼2-fold more activity than the adult (4 months) ones and also its activity is highest among the tissues. The specificity of iPPase activity in the spectrophotometric assay and in-gel analysis was confirmed by specific iPPase inhibitors like CaCl₂ and NaF.