Molecular signaling and clinical implications in the human aging-cancer cycle.

It is well documented that aging is associated with cancer, and likewise, cancer survivors display accelerated aging. As the number of aging individuals and cancer survivors continues to grow, it raises additional concerns across society. Therefore, unraveling the molecular mechanisms of aging in tissues is essential to developing effective therapies to fight the aging and cancer diseases in cancer survivors and cancer patients. Indeed, cellular senescence is a critical response, or a natural barrier to suppress the transition of normal cells into cancer cells, however, hypoxia which is physiologically required to maintain the stem cell niche, is increased by aging and inhibits senescence in tissues. Interestingly, oxygen restriction or hypoxia increases longevity and slows the aging process in humans, but hypoxia can also drive angiogenesis to facilitate cancer progression. In addition, cancer treatment is considered as one of the major reasons that drive cellular senescence, subsequently followed by accelerated aging. Several clinical trials have recently evaluated inhibitors to eliminate senescent cells. However, some mechanisms of aging typically can also retard cancer cell growth and progression, which might require careful strategy for better clinical outcomes. Here we describe the molecular regulation of aging and cancer in crosstalk with DNA damage and hypoxia signaling pathways in cancer patients and cancer survivors. We also update several therapeutic strategies that might be critical in reversing the cancer treatment-associated aging process.