Should we invest in biological age predictors to treat colorectal cancer in older adults?

Abstract

Colorectal cancer (CRC) is a chronic disease of the old population with slow development progressing into clinical signs and symptoms. Biological aging is characterized by e.g. mitochondrial dysfunction and epigenetic alterations (e.g. methylation)-mechanisms that are also important in cancer development. For CRC, specific types of tumors are distinguishable by their methylation patterns and several detection methods using different epigenetic marks have been developed as signatures for the disease. Biological age assessed by DNA methylation patterns from blood, i.e. the epigenetic clock, is higher in CRC patients compared to controls, and may be a tool for identifying individuals at increased risk for CRC. Other types of biomarkers of aging are useful to calculate biological age, such as metabolites, protein levels, inflammatory markers and clinical biomarkers, where composite scores of biomarkers have been used to assess the risk of CRC and colorectal adenomas. Clinical assessments of biological aging includes frailty, which is a geriatric syndrome characterized by increased vulnerability to adverse outcomes. More than half of the CRC patients are estimated to be frail or pre-frail, and these individuals are at increased risk of postoperative complications, poorer prognosis, treatment intolerance and death. Hence, considering frailty as part of biological age in CRC patients may help identifying those at need of close monitoring. In summary, future screening programs for CRC may make use of biological age assessments, e.g. by epigenetic clock or composite scores. Monitoring disease relapse and treatment response should be enhanced in frail individuals for better prognosis.

Genetic associations for two biological age measures point to distinct aging phenotypes

“…BA predictors may help discover drivers of the aging process and can be used for secondary prevention by identifying at-risk individuals prior to disease onset. Additionally, they have been proposed as tools to monitor intervention or treatment effects aimed at targeting the aging process 5 .…”

Promising Epigenetic Biomarkers for the Early Detection of Colorectal Cancer: A Systematic Review

“…The incidence of colorectal cancer increases with age. Biological aging is associated with genomic instability, mitochondrial dysfunction, epigenetic changes, increased cellular vulnerability, and telomeric erosion [ 12 , 13 ].…”

Immune depletion of the methylated phenotype of colon cancer is closely related to resistance to immune checkpoint inhibitors

“…Herein, using transcriptome, DNA methylation, and driver mutations of CRC, we developed a classifier based on multi-omics integration for the prognosis prediction of CRC for the first time. At present, many studies have proved that CRC is the result of accumulation of multiple gene mutations and epigenetic modifications, and DNA hypermethylation or hypomethylation can be used as epigenetic biomarkers to predict the occurrence and prognostic effects of CRC (75)(76)(77). Driver mutations in the genome can be viewed as responsible for molecular changes associated with CRC progression, so targeting such genes for the elimination of multiple CRC gene dependencies could significantly improve efficacy (78).…”