Aberrant differentiations of bone mesenchymal stem cells (BMSCs) have proved to be associated with the occurrence of senile osteoporosis. However, mechanisms of this phenomenon relative to abnormal lipid metabolism remain unclear. This study was conducted to characterize the lipidomics alterations during BMSC passaging, aiming at uncovering the aging-related lipid metabolism that may play an important role in aberrant differentiations of BMSCs. Principal component analysis presented the sequential lipidomics alterations during BMSC passaging. The majority of glycerophospholipids, including phosphatidylcholines, phosphatidylethanolamines, phosphatidylglycerols, as well as sphingolipids, revealed significant elevations, whereas the others, including phosphatidic acids, phosphatidylinositols, and phosphatidylserines, presented decreases in aged cells. Double-bond equivalent versus carbon number plots demonstrated that the changing trends and significances of lipids during passaging were associated with the chain length and the degree of unsaturation. In the correlation networks, the scattering patterns of lipid categories suggested the category-related metabolic independence and potential conversion among phosphatidic acids, phosphatidylinositols, and phosphatidylserines. The lipid-enzyme integrated pathway analysis indicated the activated metabolic conversion from phosphatidic acids to CDP-diacylglycerol to phosphatidylinositols and from sphingosine to ceramides to sphingomyelins with BMSC passaging. The conversions among lipid species described the lipidomics responses that potentially induced the aberrant differentiations during BMSC aging. © Copyright 2019 American Chemical Society.