Differential Effects of Liver Regeneration on Aging‐Related Changes in Gene Expression and Metabolic Function

Aging causes significant changes in gene expression and metabolic function of cells in various organs. Although it is known that liver regeneration is delayed by aging, the effects of aging on changes in gene expression and metabolic functions in liver regeneration need further investigation. In this study, we comprehensively analyzed changes in gene expression and metabolic function by liver regeneration in young and old mice to examine the effects of aging on these changes. During the process of liver regeneration, the gene expression profiles of hepatocytes from young and old mice changed significantly in a stepwise manner while each remained close together. After the completion of liver regeneration, the genes with aging-specific expression patterns in old mouse hepatocytes changed to expression levels close to those in young mouse hepatocytes. In contrast to the results of these transcriptome analyses, the aging-specific changes in metabolic state detected in old mouse livers were found to be largely maintained after the completion of liver regeneration. These results demonstrated that the gene expression state in the liver of old mice is flexibly altered by liver regeneration, whereas their metabolic state is robust. This finding helps to elucidate the relationship between aging and liver regeneration and to determine the basis of the increased incidence of liver disease with aging.