Decoding the tumor-aging axis: from bench to clinical
TL;DR
Mechanistic, clinical, and translational evidence defining the tumor-aging axis is synthesized and emerging strategies aimed at interrupting this pathogenic cycle are discussed.
Abstract
Population aging is a major global health challenge and a principal risk factor for cancer. Aging does not simply increase mutational burden; it reshapes tissue homeostasis across genetic, epigenetic, metabolic, immune, and systemic dimensions. Genomic instability, epigenetic drift, mitochondrial dysfunction, and metabolic rewiring collectively establish a tumor-permissive landscape that enhances clonal diversification and lowers the threshold for malignant transformation. Concurrently, accumulation of senescent cells and the senescence-associated secretory phenotype (SASP) remodel the microenvironment, promote immune suppression, and weaken tumor surveillance, further exacerbated by immunosenescence and gut microbiota dysbiosis. Importantly, cancer progression feeds back to accelerate organismal aging. Tumor burden and therapy-induced stress destabilize hematopoietic and non-hematopoietic stem cell niches, disrupt systemic metabolic homeostasis, and induce neuroendocrine reprogramming, thereby amplifying multi-organ functional decline. Aging and cancer therefore constitute a bidirectional and self-reinforcing network rather than a linear cause-effect relationship. In this review, we synthesize mechanistic, clinical, and translational evidence defining the tumor-aging axis and discuss emerging strategies aimed at interrupting this pathogenic cycle.