Pan-cancer analysis reveals unique molecular patterns associated with age

Older age is a strong risk factor for several diseases, including cancer. In cancer, older age is also frequently associated with a more aggressive, treatment-refractory tumor phenotype. The etiology and biology of age-associated differences among cancers are poorly understood. To address this knowledge gap, we sought to delineate the differences in tumor molecular characteristics between younger and older patients across a variety of tumor types. We found that tumors in younger and older patients exhibit widespread molecular differences. First, we observed that tumors in younger individuals, unlike those in older ones, exhibit an accelerated molecular aging phenotype associated with some hallmarks of premature senescence. Second, we found that tumors from younger individuals are enriched for driver gene mutations resulting in homologous recombination defects. Third, we observed a trend towards a decrease in immune infiltration and function in older patients and found that, immunologically, young tumor tissue resembles aged healthy tissue. Taken together, we find that tumors from young individuals possess unique characteristics compared to tumors in older individuals, which can potentially be leveraged for differential therapeutic strategies.