School of Health and Medical Sciences, University of Southern Queensland, Toowoomba, Queensland, Australia.
Centre for Health Research, Toowoomba, Queensland, Australia.
Physiol Genomics. 2024 Dec 1;56(12):869-875. doi: 10.1152/physiolgenomics.00075.2024. Epub 2024 Oct 7.
Cancer remains a leading cause of death worldwide and although prognosis and survivorship after therapy have improved significantly, current cancer treatments have long-term health consequences. For decades telomerase-mediated telomere maintenance has been an attractive anti-cancer therapeutic target due to its abundance and role in telomere maintenance, pathogenesis, and growth in neoplasms. Telomere maintenance-specific cancer therapies, however, are marred by off-target side effects that must be addressed before they reach clinical practice. Regular exercise training is associated with telomerase-mediated telomere maintenance in normal cells, which is associated with healthy aging. A single bout of endurance exercise training dynamically, but temporarily, increases mRNA and telomerase activity, as well as several molecules that control genomic stability and telomere length (i.e., shelterin and TERRA). Considering the epidemiological findings and accumulating research highlighting that exercise significantly reduces the risk of many types of cancers and the anti-carcinogenic effects of exercise on tumor growth , investigating the governing molecular mechanisms of telomerase control in context with exercise and cancer may provide important new insights to explain these findings. Specifically, the molecular mechanisms controlling telomerase in both healthy cells and tumors after exercise could reveal novel therapeutic targets for tumor-specific telomere maintenance and offer important evidence that may refine current physical activity and exercise guidelines for all stages of cancer care.
癌症仍然是全球主要的死亡原因,尽管治疗后的预后和存活率有了显著提高,但目前的癌症治疗方法仍有长期的健康后果。几十年来,端粒酶介导的端粒维持因其在端粒维持、发病机制和肿瘤生长中的丰富性和作用而成为一种有吸引力的抗癌治疗靶点。然而,端粒维持特异性癌症疗法存在脱靶副作用,在它们进入临床实践之前必须解决这些问题。有规律的运动训练与正常细胞中端粒酶介导的端粒维持有关,这与健康衰老有关。单次耐力运动训练会动态但暂时地增加 mRNA 和端粒酶活性,以及控制基因组稳定性和端粒长度的几种分子(即庇护素和 TERRA)。考虑到流行病学研究结果以及越来越多的研究强调运动显著降低了多种癌症的风险,以及运动对肿瘤生长的抗癌作用,研究与运动和癌症相关的端粒酶控制的调控分子机制可能为解释这些发现提供重要的新见解。具体来说,运动后健康细胞和肿瘤中控制端粒酶的分子机制可能揭示肿瘤特异性端粒维持的新治疗靶点,并提供重要证据,可能完善目前针对癌症治疗各个阶段的体力活动和运动指南。