Pathogenesis of cancer-induced cachexia in aged mice

Cancer cachexia is a progressive weight loss and functional impairment syndrome that 30-90% of cancer patients experience. Although most cancers associated with cachexia occur in older individuals, mouse models of cachexia primarily rely on young male mice. Limited studies compare cachexia inclusive of age and sex. Even fewer studies also investigate heart muscle. Older individuals have higher heart disease risk, and cachexia weakens heart function. Therefore, this study compared cancer cachexia progression in eight groups of young and old mice of both sexes with colon-26 adenocarcinoma or sham injections. Cachectic atrophy of muscle and adipose tissue occurred in both sexes and ages, however, old mice and females had reduced losses compared to young mice and males. Tumors induced significant cardiac tissue atrophy, but there was a differential effect that sex had on atrophy with females having some protection. Preliminary cardiac PCR analysis revealed an increased inflammatory environment with decreased GDF-15 and increased IL-6 expression in tumor-bearing mice, giving insight into cardiac pathology. Older mice also had greater GDF-15 expression than young mice. In conclusion, preclinical models produced a similar wasting phenotype between sexes and ages, however, young mice have a more exacerbated and consistent phenotype. Utilizing cachexia mouse models that are representative of the human condition is important in future research and clinical care for patients with cancer cachexia.