Brain aging and garbage cleaning
Brain aging and garbage cleaning
复制标题
大脑老化与垃圾清理
DOI：
--
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发表时间：
2020
影响因子：
9
通讯作者：
C. Franceschi
中科院分区：
文献类型：
--
作者：
S. Gordleeva;O. Kanakov;M. Ivanchenko;A. Zaikin;C. Franceschi
大脑老化是一个复杂的过程，涉及我们身体的许多功能，并通过睡眠模式和由小胶质细胞功能和胶质淋巴系统调节的代谢废物浓度变化的相互作用来描述。我们回顾了现有的建模方法，这一主题，并得出一个新的数学模型来描述这些组件之间的串扰的概念框架内炎症。对该模型的分析可以深入了解垃圾浓度的动态变化以及由正常或中断的睡眠模式引起的相关小胶质细胞衰老过程，从而解释健康或不健康大脑衰老背后的潜在机制。该模型结合了垃圾的积累和消除，垃圾诱导胶质细胞活化，过度活化诱导胶质细胞衰老，以及衰老相关分泌表型（SASP）产生促炎分子。假设睡眠不足导致垃圾浓度增加并促进衰老，该模型预测，如果衰老神经胶质细胞的积累超过炎症阈值，即使恢复正常的睡眠模式，衰老的进一步进展也变得不可阻挡。通过“恢复大脑活力”来逆转这一过程，只有通过将衰老神经胶质的浓度重置到低于这一阈值才有可能。我们的模型方法能够分析衰老的时空动力学，通过这种方式，我们表明炎症的异质模式将加速衰老曲线通过网络的传播，证实异质性的负面影响。
Brain aging is a complex process involving many functions of our body and described by the interplay of a sleep pattern and changes in the metabolic waste concentration regulated by the microglial function and the glymphatic system. We review the existing modelling approaches to this topic and derive a novel mathematical model to describe the crosstalk between these components within the conceptual framework of inflammaging. Analysis of the model gives insight into the dynamics of garbage concentration and linked microglial senescence process resulting from a normal or disrupted sleep pattern, hence, explaining an underlying mechanism behind healthy or unhealthy brain aging. The model incorporates accumulation and elimination of garbage, induction of glial activation by garbage, and glial senescence by over-activation, as well as the production of pro-inflammatory molecules by their senescence-associated secretory phenotype (SASP). Assuming that insufficient sleep leads to the increase of garbage concentration and promotes senescence, the model predicts that if the accumulation of senescent glia overcomes an inflammaging threshold, further progression of senescence becomes unstoppable even if a normal sleep pattern is restored. Inverting this process by “rejuvenating the brain” is only possible via a reset of concentration of senescent glia below this threshold. Our model approach enables analysis of space-time dynamics of senescence, and in this way, we show that heterogeneous patterns of inflammation will accelerate the propagation of senescence profile through a network, confirming a negative effect of heterogeneity.
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DOI：
10.1016/j.beem.2010.08.014
发表时间：
2010-10
期刊：
Best practice & research. Clinical endocrinology & metabolism
影响因子：
--
作者：
Mullington JM;Simpson NS;Meier-Ewert HK;Haack M
通讯作者：
Haack M
影响因子：
7.3
作者：
Pezze, Piero Dalle;Sonntag, Annika G.;Thedieck, Kathrin
通讯作者：
Thedieck, Kathrin
影响因子：
18.2
作者：
Campisi J
通讯作者：
Campisi J
影响因子：
16.6
作者：
Labbadia J;Morimoto RI
通讯作者：
Morimoto RI
端粒缩短的随机模型。
影响因子：
4.3
作者：
Olofsson,P;Kimmel,M
通讯作者：
Kimmel,M