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肿瘤与衰老互作的基础研究进展与临床启示
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Abstract:
恶性肿瘤是本世纪最严重威胁人类生命与健康的重大疾病之一，深入探究其发生与发展机制具有重要的科学意义和临床价值。机体衰老不仅是肿瘤发生发展的重要诱因，同时肿瘤的发展又会反过来加剧机体衰老，二者共同构成了双向恶性循环的肿瘤–衰老轴。一方面，衰老引发的基因组不稳定的增加、衰老相关分泌表型分子(SASP)的释放、机体免疫功能的衰退和肠道菌群的失衡等因素，均可促进肿瘤的发生发展；另一方面，肿瘤的演进及治疗过程会进一步诱导炎症因子和细胞外囊泡的释放，驱动慢性炎症反应，从而加速机体的衰老。在本综述中，我们将系统梳理肿瘤–衰老轴的核心内涵，总结衰老在肿瘤发生发展中的关键作用机制，阐述肿瘤及其治疗如何加速机体衰老进程，并进一步探讨靶向肿瘤–衰老轴干预策略及其潜在前景与挑战。
Malignant tumors represent one of the most critical threats to human life and health in this century. A deeper understanding of the mechanisms underlying their initiation and progression is of great scientific and clinical importance. Organismal aging is not only a major predisposing factor for tumor development but is also exacerbated by tumor progression, together forming a bidirectional vicious cycle referred to as the tumor-aging axis. On one hand, aging-related factors, including increased genomic instability, the release of senescence-associated secretory phenotype (SASP) molecules, declining immune function, and gut microbiota dysbiosis, collectively promote tumor initiation and progression. On the other hand, tumor evolution and anticancer treatments further induce the release of inflammatory cytokines and extracellular vesicles, fueling chronic inflammatory responses that accelerate systemic aging. In this review, we systematically outline the core concepts of the tumor-aging axis, summarize key mechanisms by which aging influences tumor development, elucidate how tumors and their treatments drive aging, and discuss potential intervention strategies targeting this axis, along with their prospects and challenges.
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