Suppr超能文献

SIRT1 通过一种随年龄衰减的机制介导 SCN 中的中枢生物钟控制。

SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging.

机构信息

Glenn Laboratory for the Science of Aging, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

出版信息

Cell. 2013 Jun 20;153(7):1448-60. doi: 10.1016/j.cell.2013.05.027.

Abstract

SIRT1 is a NAD(+)-dependent protein deacetylase that governs many physiological pathways, including circadian rhythm in peripheral tissues. Here, we show that SIRT1 in the brain governs central circadian control by activating the transcription of the two major circadian regulators, BMAL1 and CLOCK. This activation comprises an amplifying circadian loop involving SIRT1, PGC-1α, and Nampt. In aged wild-type mice, SIRT1 levels in the suprachiasmatic nucleus are decreased, as are those of BMAL1 and PER2, giving rise to a longer intrinsic period, a more disrupted activity pattern, and an inability to adapt to changes in the light entrainment schedule. Young mice lacking brain SIRT1 phenocopy these aging-dependent circadian changes, whereas mice that overexpress SIRT1 in the brain are protected from the effects of aging. Our findings indicate that SIRT1 activates the central pacemaker to maintain robust circadian control in young animals, and a decay in this activity may play an important role in aging.

摘要

SIRT1 是一种依赖 NAD(+)的蛋白去乙酰化酶,它调控着许多生理途径,包括外周组织的生物钟节律。在这里,我们发现大脑中的 SIRT1 通过激活两个主要生物钟调节剂 BMAL1 和 CLOCK 的转录来控制中枢生物钟的控制。这种激活包含一个涉及 SIRT1、PGC-1α 和 Nampt 的放大生物钟循环。在老年野生型小鼠中,视交叉上核中的 SIRT1 水平下降,BMAL1 和 PER2 的水平也下降,导致内在周期变长、活动模式更加紊乱,并且无法适应光适应时间表的变化。缺乏大脑 SIRT1 的年轻小鼠表现出与这些与年龄相关的生物钟变化相似的表型,而在大脑中过表达 SIRT1 的小鼠则能免受衰老的影响。我们的研究结果表明,SIRT1 激活中枢起搏器以维持年轻动物中强大的生物钟控制,而这种活性的衰减可能在衰老中起着重要作用。

相似文献

1
SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging.
Cell. 2013 Jun 20;153(7):1448-60. doi: 10.1016/j.cell.2013.05.027.
2
Computational and experimental insights into the circadian effects of SIRT1.
Proc Natl Acad Sci U S A. 2018 Nov 6;115(45):11643-11648. doi: 10.1073/pnas.1803410115. Epub 2018 Oct 22.
3
SIRT1 regulates circadian clock gene expression through PER2 deacetylation.
Cell. 2008 Jul 25;134(2):317-28. doi: 10.1016/j.cell.2008.06.050.
4
Role of miR-142-3p in the post-transcriptional regulation of the clock gene Bmal1 in the mouse SCN.
PLoS One. 2013 Jun 5;8(6):e65300. doi: 10.1371/journal.pone.0065300. Print 2013.
6
Aging well with a little wine and a good clock.
Cell. 2013 Jun 20;153(7):1421-2. doi: 10.1016/j.cell.2013.05.055.
8
CLOCK and BMAL1 Regulate Muscle Insulin Sensitivity via SIRT1 in Male Mice.
Endocrinology. 2016 Jun;157(6):2259-69. doi: 10.1210/en.2015-2027. Epub 2016 Apr 1.
9
Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1.
Science. 2009 May 1;324(5927):654-7. doi: 10.1126/science.1170803. Epub 2009 Mar 12.
10
The circadian pacemaker in the cultured suprachiasmatic nucleus from pup mice is highly sensitive to external perturbation.
Eur J Neurosci. 2008 May;27(10):2686-90. doi: 10.1111/j.1460-9568.2008.06231.x. Epub 2008 May 29.

引用本文的文献

1
Protein Acetylation and NAD+ Homeostasis in Aging Muscle.
Adv Exp Med Biol. 2025;1478:421-443. doi: 10.1007/978-3-031-88361-3_17.
2
Circadian Rhythm Cascade SIRT1/PGC-1α/BMAL1 Pathway Regulates Nitroglycerin-Induced Chronic Migraine.
Neurochem Res. 2025 Aug 13;50(4):262. doi: 10.1007/s11064-025-04513-9.
5
Linkage of circadian rhythm disruptions with Alzheimer's disease and therapeutic interventions.
Acta Pharm Sin B. 2025 Jun;15(6):2945-2965. doi: 10.1016/j.apsb.2025.04.011. Epub 2025 Apr 15.
6
The circadian clock, metabolism, and inflammation-the holy trinity of inflammatory bowel diseases.
Clin Sci (Lond). 2025 Jul 4;139(13):777-90. doi: 10.1042/CS20256383.
7
Circadian clock and its effect on aging and lifespan.
Biogerontology. 2025 Jun 27;26(4):132. doi: 10.1007/s10522-025-10281-4.
9
Unraveling the interplay between sleep, redox metabolism, and aging: implications for brain health and longevity.
Front Aging. 2025 May 21;6:1605070. doi: 10.3389/fragi.2025.1605070. eCollection 2025.

本文引用的文献

1
Pharmacological modulation of circadian rhythms by synthetic activators of the deacetylase SIRT1.
Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3333-8. doi: 10.1073/pnas.1214266110. Epub 2013 Jan 22.
2
Deviation of innate circadian period from 24 h reduces longevity in mice.
Aging Cell. 2012 Oct;11(5):794-800. doi: 10.1111/j.1474-9726.2012.00846.x. Epub 2012 Jul 12.
3
Rev-erbα and Rev-erbβ coordinately protect the circadian clock and normal metabolic function.
Genes Dev. 2012 Apr 1;26(7):657-67. doi: 10.1101/gad.186858.112.
4
Regulation of circadian behaviour and metabolism by REV-ERB-α and REV-ERB-β.
Nature. 2012 Mar 29;485(7396):123-7. doi: 10.1038/nature11048.
5
The circadian clock and pathology of the ageing brain.
Nat Rev Neurosci. 2012 Mar 7;13(5):325-35. doi: 10.1038/nrn3208.
6
Sirtuins and calorie restriction.
Nat Rev Mol Cell Biol. 2012 Feb 29;13(4):207. doi: 10.1038/nrm3308.
7
PML regulates PER2 nuclear localization and circadian function.
EMBO J. 2012 Mar 21;31(6):1427-39. doi: 10.1038/emboj.2012.1. Epub 2012 Jan 24.
8
SIRT1 protects against α-synuclein aggregation by activating molecular chaperones.
J Neurosci. 2012 Jan 4;32(1):124-32. doi: 10.1523/JNEUROSCI.3442-11.2012.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验