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

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.