Aging and cancer: current understandings and future perspectives

Deciphering the mechanistic links between aging and cancer remains a central challenge in biomedical research. This review begins by presenting recent epidemiological data on cancer incidence across age groups, underscoring the complex and paradoxical interplay between aging and cancer. A systematic analysis follows four core signaling pathways that underpin both aging and cancer: (i) nutrient sensing and energy metabolism pathways, (ii) stress response and genome maintenance pathways, (iii) inflammatory and microenvironmental pathways, and (iv) sirtuin-mediated epigenetic and transcriptional modulation pathways. Each pathway is analyzed regarding its distinct and overlapping roles in aging and cancer, with exploration of strategies for comodulating these shared mechanisms to simultaneously mitigate both conditions. Established and emerging druggable targets within these pathways are highlighted, offering new perspectives for future therapeutic development. Current integrative strategies to achieve concurrent antiaging and anticancer effects include targeting cellular nutrient sensing and metabolism, enhancing genomic integrity, suppressing chronic inflammation, clearing senescent cells, and modulating epigenetic programs. Finally, the impact of aging on cancer therapy, particularly immunotherapy, is discussed, along with a review of representative aging-related pathways and genes and their roles in modulating immunotherapy efficacy. Analysis of agents targeting each pathway spanning preclinical studies, clinical trials, and clinically approved drugs reveals disparities in the research progress between anti-aging and anticancer applications. Consequently, a promising future strategy for drug discovery lies in repurposing well-established anticancer agents for antiaging interventions, as well as translating insights from aging research into novel antitumor therapies, thereby achieving synergistic benefits in both fields.