Ahmed Rezwana, Nakahata Yasukazu, Shinohara Kazuyuki, Bessho Yasumasa
Laboratory of Gene Regulation Research, Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology (NAIST), Ikoma, Japan.
Department of Neurobiology and Behavior, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Front Neurosci. 2021 Jan 25;15:638122. doi: 10.3389/fnins.2021.638122. eCollection 2021.
Senescent cells, which show the permanent growth arrest in response to various forms of stress, accumulate in the body with the progression of age, and are associated with aging and age-associated diseases. Although the senescent cells are growth arrested, they still demonstrate high metabolic rate and altered gene expressions, indicating that senescent cells are still active. We recently showed that the circadian clock properties, namely phase and period of the cells, are altered with the establishment of replicative senescence. However, whether cellular senescence triggers the alteration of circadian clock properties in the cells is still unknown. In this study we show that the oxidative stress-induced premature senescence induces the alterations of the circadian clock, similar to the phenotypes of the replicative senescent cells. We found that the oxidative stress-induced premature senescent cells display the prolonged period and delayed phases. In addition, the magnitude of these changes intensified over time, indicating that cellular senescence changes the circadian clock properties. Our current results corroborate with our previous findings and further confirm that cellular senescence induces altered circadian clock properties, irrespective of the replicative senescence or the stress-induced premature senescence.
衰老细胞会因各种形式的应激而出现永久性生长停滞，随着年龄的增长在体内积累，并与衰老及年龄相关疾病有关。尽管衰老细胞生长停滞，但它们仍表现出高代谢率和基因表达改变，这表明衰老细胞仍然活跃。我们最近发现，随着复制性衰老的建立，细胞的昼夜节律特性，即细胞的相位和周期会发生改变。然而，细胞衰老是否会触发细胞内昼夜节律特性的改变仍不清楚。在这项研究中，我们表明氧化应激诱导的早衰会导致昼夜节律的改变，类似于复制性衰老细胞的表型。我们发现，氧化应激诱导的早衰细胞表现出周期延长和相位延迟。此外，这些变化的程度会随着时间的推移而加剧，表明细胞衰老会改变昼夜节律特性。我们目前的结果与我们之前的发现一致，并进一步证实，无论复制性衰老还是应激诱导的早衰，细胞衰老都会导致昼夜节律特性改变。
