Patel Parthive H, Tamanoi Fuyuhiko
Molecular Biology Institute, Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095-1489, USA.
J Cell Sci. 2006 Oct 15;119(Pt 20):4285-92. doi: 10.1242/jcs.03199.
The accumulation of free radical damage to an organism over its lifespan can cause premature aging and disease including cancer, atherosclerosis and neurodegenerative disorders. The well-conserved Rheb-Target-of-rapamycin (TOR)-S6-kinase (S6K) signaling pathway regulates several cellular processes and has been shown to influence lifespan and diseases such as cancer and neurodegenerative disorders. Using adult Drosophila, we describe for the first time in metazoans that TOR activity can influence the stress response. We find that mildly increasing systemic Rheb-TOR-S6K signaling sensitizes the whole organism to oxidative stress and promotes senescence of locomotor activity with age. Furthermore, we find that S6K is required for increased Rheb-TOR signaling to sensitize the whole organism to oxidative stress and promote the senescence of locomotor activity. Interestingly, we also find that increasing Rheb-TOR signaling in muscle can increase the sensitivity of adults to oxidative stress. These data imply that pathological situations that increase TOR activity might perturb the ability of the whole organism to cope with stress causing disease progression and aging.
自由基对生物体一生的损害积累会导致过早衰老和疾病，包括癌症、动脉粥样硬化和神经退行性疾病。高度保守的Rheb-雷帕霉素靶蛋白（TOR）-S6激酶（S6K）信号通路调节多种细胞过程，并已被证明会影响寿命以及癌症和神经退行性疾病等病症。利用成年果蝇，我们首次在多细胞动物中描述了TOR活性可影响应激反应。我们发现，适度增加全身的Rheb-TOR-S6K信号会使整个生物体对氧化应激敏感，并随着年龄增长促进运动活性的衰老。此外，我们发现增加的Rheb-TOR信号要使整个生物体对氧化应激敏感并促进运动活性的衰老，S6K是必需的。有趣的是，我们还发现增加肌肉中的Rheb-TOR信号会增加成年果蝇对氧化应激的敏感性。这些数据表明，增加TOR活性的病理情况可能会扰乱整个生物体应对压力的能力，从而导致疾病进展和衰老。
