Senotherapy: growing old and staying young?
Senotherapy: growing old and staying young?
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DOI：
10.1007/s00424-017-1972-4
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发表时间：
2017-04
期刊：
影响因子：
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通讯作者：
R. Schmitt
中科院分区：
文献类型：
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作者：
R. Schmitt
细胞衰老与年龄相关的疾病有关，发生在正常衰老或病理性细胞应激的结果。由于它们不能增殖，衰老的细胞不能对正常的组织维持和组织修复做出贡献。相反，衰老细胞通过分泌过多的生物活性因子来扰乱微环境，这些生物活性因子可能导致炎症、再生功能障碍和肿瘤进展。最近对诱导和维持细胞衰老的刺激和途径的了解提供了选择性地消除衰老细胞的可能性。这种到目前为止还没有在人体上进行测试的新策略，被称为感觉疗法或感觉化疗法。在小鼠身上，情感疗法被证明在加速衰老模型和正常的时间衰老过程中都有效。老年疗法可以延长寿命，恢复骨髓、肌肉和皮肤祖细胞的功能，改善血管舒缩功能，减缓动脉粥样硬化的进展。虽然最初的研究使用遗传方法来杀死衰老细胞，但最近的方法显示了与衰老药物类似的效果。这些观察打开了令人兴奋的可能性，具有巨大的临床开发潜力。然而，在考虑将老年疗法整合到患者护理中之前，我们需要进一步的研究，以提高我们对这一策略在短期和长期使用期间的安全性和有效性的洞察力。
Cellular senescence, which has been linked to age-related diseases, occurs during normal aging or as a result of pathological cell stress. Due to their incapacity to proliferate, senescent cells cannot contribute to normal tissue maintenance and tissue repair. Instead, senescent cells disturb the microenvironment by secreting a plethora of bioactive factors that may lead to inflammation, regenerative dysfunction and tumor progression. Recent understanding of stimuli and pathways that induce and maintain cellular senescence offers the possibility to selectively eliminate senescent cells. This novel strategy, which so far has not been tested in humans, has been coined senotherapy or senolysis. In mice, senotherapy proofed to be effective in models of accelerated aging and also during normal chronological aging. Senotherapy prolonged lifespan, rejuvenated the function of bone marrow, muscle and skin progenitor cells, improved vasomotor function and slowed down atherosclerosis progression. While initial studies used genetic approaches for the killing of senescent cells, recent approaches showed similar effects with senolytic drugs. These observations open up exciting possibilities with a great potential for clinical development. However, before the integration of senotherapy into patient care can be considered, we need further research to improve our insight into the safety and efficacy of this strategy during short- and long-term use.