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In humans, age and adiposity are major risk factors for malignancies, but most genetically engineered mouse models (GEMM) induce carcinogenesis too rapidly to study these influences. Standard strains, such as C57BL\/6, commonly used in GEMMs, further limit the exploration of aging and metabolic health effects. A similar challenge arises in modeling periodontitis, a disease influenced by aging, diabesity, and genetic architecture. We propose using diverse mouse populations with hybrid vigor, such as the Collaborative Cross (CC)\u2009\u00d7\u2009<jats:italic>Apc<\/jats:italic><jats:sup><jats:italic>Min<\/jats:italic><\/jats:sup> hybrid, to slow disease progression and better model human colorectal cancer (CRC) and comorbidities. This perspective highlights the advantages of this model, where delayed carcinogenesis reveals interactions with aging and adiposity. Unlike <jats:italic>Apc<\/jats:italic><jats:sup><jats:italic>Min<\/jats:italic><\/jats:sup> mice, which develop cancer rapidly, CC\u2009\u00d7\u2009<jats:italic>Apc<\/jats:italic><jats:sup><jats:italic>Min<\/jats:italic><\/jats:sup> hybrids recapitulate human\u2010like progression. This facilitates the identification of modifier loci affecting inflammation, diet susceptibility, organ size, and polyposis distribution. The CC\u2009\u00d7\u2009<jats:italic>Apc<\/jats:italic><jats:sup><jats:italic>Min<\/jats:italic><\/jats:sup> model offers a transformative platform for studying CRC as a disease of adulthood, reflecting its complex interplay with aging and comorbidities. The insights gained from this approach will enhance early detection, management, and treatment strategies for CRC and related conditions.<\/jats:p>","DOI":"10.1002\/ame2.12568","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T10:27:21Z","timestamp":1739269641000},"page":"758-770","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["System genetic analysis of intestinal cancer and periodontitis development as influenced by aging and diabesity using Collaborative Cross mice"],"prefix":"10.1002","volume":"8","author":[{"given":"Iqbal M.","family":"Lone","sequence":"first","affiliation":[{"name":"Department of Clinical Microbiology and Immunology, Faculty of Medicine and Health Sciences Tel Aviv University  Tel\u2010Aviv 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