Stress granules (SGs) are membraneless organelles formed in response to insult. These granules are related to pathological granules found in age-related neurogenerative diseases such as Parkinson’s and Alzheimer’s. Previously, we demonstrated that senescent cells, which accumulate with age, exposed to chronic oxidative stress, are unable to form SGs. Here, we show that the senescent cells’ inability to form SGs correlates with an upregulation in both the heat-shock response and autophagy pathways, both of which are well-established promoters of SG disassembly. Our data also reveals that the knockdown of HSP70 and ATG5, important components of the heat-shock response and autophagy pathways, respectively, restores the number of SGs formed in senescent cells exposed to chronic oxidative stress. Surprisingly, under these conditions, the depletion of HSP70 or ATG5 did not affect the clearance of these SGs during their recovery from chronic stress. These data reveal that senescent cells possess a unique heat-shock and autophagy-dependent ability to impair the formation of SGs in response to chronic stress, thereby expanding the existing understanding of SG dynamics in senescent cells and their potential contribution to age-related neurodegenerative diseases.

应力颗粒 (SGs) 是在受到伤害时形成的无膜细胞器。这些颗粒与年龄相关的神经元疾病（如帕金森氏症和阿尔茨海默氏症）中发现的病理颗粒有关。以前，我们证明了随着年龄的增长而积累的衰老细胞，暴露于慢性氧化应激，无法形成 SG。在这里，我们表明衰老细胞无法形成 SGs 与热休克反应和自噬途径的上调相关，这两者都是 SG 分解的公认启动子。我们的数据还表明，热休克反应和自噬途径的重要组成部分 HSP70 和 ATG5 的敲低分别恢复了暴露于慢性氧化应激的衰老细胞中形成的 SGs 的数量。令人惊讶的是，在这些条件下，HSP70 或 ATG5 的消耗不影响这些 SG 在从慢性压力中恢复期间的清除。这些数据表明，衰老细胞具有独特的热休克和自噬依赖性能力，可以损害响应慢性压力的 SGs 的形成，从而扩展对衰老细胞中 SG 动态及其对年龄相关神经退行性疾病的潜在贡献的现有理解.