Reorganization of pancreas circadian transcriptome with aging
The evolutionarily conserved circadian system allows organisms to synchronize internal processes with 24-h cycling environmental timing cues, ensuring optimal adaptation. Like other organs, the pancreas function is under circadian control. Recent evidence suggests that aging by itself is associated with altered circadian homeostasis in different tissues which could affect the organ's resiliency to aging-related pathologies. Pancreas pathologies of either endocrine or exocrine components are age-related. Whether pancreas circadian transcriptome output is affected by age is still unknown. To address this, here we profiled the impact of age on the pancreatic transcriptome over a full circadian cycle and elucidated a circadian transcriptome reorganization of pancreas by aging. Our study highlights gain of rhythms in the extrinsic cellular pathways in the aged pancreas and extends a potential role to fibroblast-associated mechanisms. Overall design: Here we carried out a 24-h circadian transcriptomic analysis of pancreas from male mice at young and old ages. We define a comprehensive circadian transcriptome landscape and identify biological pathways that are reflective of aging pancreas. Additionally, analysis of pancreatic microenvironment revealed novel mechanistic insights into the fibroblast mediated regulation of rhythmicity in aged pancreas. We suggest that circadian transcriptome in aging pancreas re-organizes in response to age-specific signals from the cellular microenvironment, primarily modulated by fibroblasts.