Circadian-affected tissue specificity is linked to aging and longevity [sleep deprivation experiment]

Tissue specificity is a fundamental property of an organ that affects numerous biological processes, including aging and longevity, and is regulated by the circadian clock. However, the distinction between circadian-affected tissue specificity and other tissue specificities remains poorly understood. Here, using multi-omics data on circadian rhythms in mice, we discovered that approximately 35% of tissue-specific genes are directly affected by circadian regulation. These circadian-affected tissue-specific genes have higher expression levels and are associated with metabolism and hepatocyte cells. They also exhibit specific features in long-reads sequencing data. Notably, these genes are associated with aging and longevity at both the gene level and at the network module level. The expression of these genes oscillates in response to caloric and time-restricted feeding regimens, which have been demonstrated to promote longevity. In addition, aging and longevity genes are disrupted in various circadian disorders. Our study indicates that the modulation of circadian-affected tissue specificity is essential for understanding the circadian mechanisms that regulate aging and longevity at the genomic level. Overall design: The sleep deprivation experiment followed previously reported protocols (Lu et al. 2021). Mice were randomly assigned to either the experimental or control group. The experimental group was subjected to a sleep deprivation instrument, which involved forced locomotion through a slowly rotating drum (40 cm in diameter, 0.4 m per min) while having access to food and water. All mice in experimental group were placed in the sleep deprivation device for 10 h (6:00 AM–4:00 PM) during their normal resting phase while the control animals were undisturbed. Then we collected two replicates of 4 peripheral circadian tissues (forebrain, cerebellum, liver, kidney) were obtained at next six circadian time (CT) points with an interval of 4 h (CT4, CT8, CT12, CT16, CT20, and CT24)