Faculty, Staff and Student Publications
Publication Date
1-17-2025
Journal
iScience
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide, with rising prevalence among younger adults. Several lifestyle factors, particularly disruptions in circadian rhythms by light-dark (LD) shifts, are known to increase CRC risk. Epidemiological studies previously showed LD-shifts are associated with increased risk of CRC. To explore the mechanisms and interactions between LD-shift and intestinal aging, we investigated how the combination of LD-shifts and aging impacts colon carcinogenesis development. Our data showed that LD-shifts and aging increased colon tumorigenesis. Notably, LD-shift accelerated intestinal aging by altering aging-related pathways, such as intestinal barrier damage, accompanied by dysbiotic changes in the intestinal microbiota that negatively impacts barrier stability. The increased carcinogenesis and intestinal aging were preceded by enrichment in host-microbiome features that are strongly regulated by the circadian clock. Overall, our results suggest that LD-shifts, increasingly prevalent among young adults, contribute to both intestinal aging and the development of colon carcinogenesis.
Keywords
Cell biology, Cancer
DOI
10.1016/j.isci.2024.111560
PMID
39811661
PMCID
PMC11731866
PubMedCentral® Posted Date
12-9-2024
PubMedCentral® Full Text Version
Post-print
Graphical Abstract
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Gastroenterology Commons, Medical Sciences Commons, Oncology Commons