Aging induces a distinct gene expression program in mouse islets

作者：Rankin Matthew M; Kushner Jake A^*

来源：Islets, 2010, 2(6): 345-352.

DOI：10.4161/isl.2.6.13376

• islets
• regeneration
• aging
• gene expression
• beta-cells
• reg genes

The role of aging in the pathogenesis of type 2 diabetes remains poorly understood. In the past adult beta-cells were assumed to undergo frequent turnover. However, we find that beta-cell turnover declines to very low levels in middle-aged mice. We therefore hypothesized that aged islets could exhibit a distinct gene expression program. We compared gene expression in islets from young mice to islets from aged mice under basal conditions. Aging was associated with differential expression of many genes in islets, including mRNAs encoding for chromatin remodeling components, RNA binding proteins and pancreatic endocrine transcription factors. We previously observed that cell cycle entry of beta-cells is severely restricted by middle age, with minimal of beta-cell proliferation in response to regenerative stimuli such as 50% partial pancreatectomy. To characterize the effect of age in adaptive beta-cell proliferation, we measured gene expression in islets from young mice after pancreatectomy. As expected, partial pancreatectomy induced differential expression of many genes, including those encoding Reg (regenerating) proteins. Surprisingly, partial pancreatectomy also induced expression of Reg genes in islets from aged mice, which have greatly reduced capacity for adaptive beta-cell proliferation. However, there was little overlap (besides the Reg genes) in between the partial pancreatectomy induced islet genes in young mice versus old mice. Thus, partial pancreatectomy does not induce the same gene expression program in young mice vs. old mice. Taken together, our results reveal that aged islets exhibit a unique gene expression signature that could contribute to the limited regenerative capacity of mature beta-cells.

• 出版日期2010-12