The accumulation of mutations is not the only connection between aging and cancer.  Mounting evidence indicates that the aging tissue microenvironment actively selects and promotes the progression of mutant cells towards malignancies. We hypothesize that age-related metabolic changes play a key role in this process. Building on our recent findings (Maus et al. Nature Metabolism, 2023), we investigate how disrupted iron metabolism in the aged tissue microenvironment promotes inflammation, and micronutrient shortages, subsequently diverting the differentiation trajectory and fitness landscape of precancerous cells in the bone marrow and colon towards malignancy. Our goal is to develop methods that can non-invasively locate high-risk sites for cancer development, and therapeutics that can rejuvenate the tissue microenvironment thereby combating cancer.