Raynes Rachel, Juarez Crystal, Pomatto Laura C D, Sieburth Derek, Davies Kelvin J A
Leonard Davis School of Gerontology.
Zilkha Neurogenetic Institute, Keck School of Medicine, and.
J Gerontol A Biol Sci Med Sci. 2017 Feb;72(2):143-151. doi: 10.1093/gerona/glw093. Epub 2016 Jun 23.
Aging is marked by a collapse of protein homeostasis and deterioration of adaptive stress responses that often lead to disease. During aging, the induction of stress responses decline along with protein quality control. Here, we have shown that the ability to mount an adaptive response by pretreatment with minor oxidative stress is abrogated in aged Caenorhabditis elegans We have identified a defect in SKN-1 signaling sensitivity during aging and have also found an aging-related increase in basal proteasome expression and in vitro activity, however, adaptation of the 20S proteasome in response to stress is lost in old animals. Interestingly, increased activation of SKN-1 promotes stress resistance, but is unable to rescue declining adaptation during aging. Our data demonstrate that the aging-dependent decline in SKN-1 signaling negatively impacts adaptation of the 20S proteasome in response to acute oxidative stress.
衰老的特征是蛋白质稳态的崩溃和适应性应激反应的恶化，这常常导致疾病。在衰老过程中，应激反应的诱导随着蛋白质质量控制而下降。在这里，我们已经表明，在衰老的秀丽隐杆线虫中，通过轻微氧化应激预处理来产生适应性反应的能力被消除了。我们已经确定了衰老过程中SKN-1信号敏感性的缺陷，并且还发现了与衰老相关的基础蛋白酶体表达和体外活性的增加，然而，在老年动物中，20S蛋白酶体对应激的适应性丧失了。有趣的是，SKN-1的激活增加促进了应激抗性，但无法挽救衰老过程中下降的适应性。我们的数据表明，衰老依赖性的SKN-1信号下降对20S蛋白酶体对应激的适应性产生负面影响。
