Cdk4 is a critical regulator of age-associated hepatic steatosis.

Purpose: to identify the impact of cdk4 inhibition on genes and pathways involved in age-associated liver disorders using next generation sequencing on young and control- or PD0332991-treated aged mice.Methods: RNA was isolated from livers of young (2 month old) and old (20-22 month old) C57Bl6 mice. Old mice were either either control-aged mice or PD-0332991 treated aged mice (450mg/dk for 2 weeks). The three conditions were represented in triplicate. Raw reads passing quality filtration were aligned to the mm10 mouse genome using UCSC annotations by pseudoalignment in Kallisto. All reasonably expressed transcripts were submitted for statistical analysis to identify age-altered transcripts corrected by cdk4 inhibition.Results: We mapped a minimum of 20 million reads per sample, which corresponded to a total of 25,240 transcripts. Of these, 12,551 were considered reasonably expressed and were included in analysis comparing control-aged v young and PD0332991-treated-aged v young.Conclusion: Inhibition of cdk4 in ages wildtype mice by cdk4 inhibitor PD-0332991 reduces CEBPa-p300 and reduced aged-related alterations of hepatic structure and function.