Age-associated changes in microglia activation and Sirtuin-1- chromatin binding patterns.
Age-associated changes in microglia activation and Sirtuin-1- chromatin binding patterns.
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DOI：
10.18632/aging.204329
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发表时间：
2022-10-10
期刊：
影响因子：
5.2
通讯作者：
Marcondes, Maria Cecilia Garibaldi
中科院分区：
文献类型：
--
作者：
Basova, Liana, V;Bortell, Nikki;Conti, Bruno;Fox, Howard S.;Milner, Richard;Marcondes, Maria Cecilia Garibaldi
衰老过程与维持生理机制的变化有关，受遗传和生活方式的影响，并影响晚年生活质量和寿命。大脑健康对健康老龄化至关重要。Sirtuin 1（Sirt 1）是一种具有沉默特性的组蛋白脱乙酰酶，是实验上与健康和长寿相关的分子决定因素之一。我们比较了2组老年恒河猴的脑发病机制和脑前额叶皮质中Sirt 1-染色质结合动力学，按尸检年龄划分：寿命较短的动物（18-20岁（yo）），相当于60-70人yo;寿命较长的动物（23-29 yo），相当于80-100人yo并模拟成功衰老。这些与年轻的成年人的大脑（4-7岁）进行了比较。我们的研究结果表明，小胶质细胞标志物Iba 1，沿着影响Sirt 1水平和活性的因素，如CD 38（一种控制Sirt 1活性的限制NAD的酶）和mir 142（一种靶向Sirt 1转录的微小RNA）在老年组之间存在显著差异。Iba 1在短寿命动物中低于其他组，而CD 38在两个老龄组中均高于年轻组。mir 142和Sirt 1水平在较长寿命的大脑（> 23岁）中呈负相关，但在较短寿命的大脑（18-20岁）中不相关。我们还发现，与寿命较短的动物相比，Sirt 1结合在与核活性和衰老相关的基因中表现出更好的效率。总的来说，神经炎症和Sirt 1与染色质相互作用的差异区分了寿命较短和寿命较长的动物，这表明保护小胶质细胞和Sirt 1功能效率对长寿的重要性。
The aging process is associated with changes in mechanisms maintaining physiology, influenced by genetics and lifestyle, and impacting late life quality and longevity. Brain health is critical in healthy aging. Sirtuin 1 (Sirt1), a histone deacetylase with silencing properties, is one of the molecular determinants experimentally linked to health and longevity. We compared brain pathogenesis and Sirt1-chromatin binding dynamics in brain pre-frontal cortex from 2 groups of elder rhesus macaques, divided by age of necropsy: shorter-lived animals (18-20 years old (yo)), equivalent to 60-70 human yo; and longer-lived animals (23-29 yo), corresponding to 80-100 human yo and modeling successful aging. These were compared with young adult brains (4-7 yo). Our findings indicated drastic differences in the microglia marker Iba1, along with factors influencing Sirt1 levels and activity, such as CD38 (an enzyme limiting NAD that controls Sirt1 activity) and mir142 (a microRNA targeting Sirt1 transcription) between the elder groups. Iba1 was lower in shorter-lived animals than in the other groups, while CD38 was higher in both aging groups compared to young. mir142 and Sirt1 levels were inversely correlated in longer-lived brains (>23yo), but not in shorter-lived brains (18-20 yo). We also found that Sirt1 binding showed signs of better efficiency in longer-lived animals compared to shorter-lived ones, in genes associated with nuclear activity and senescence. Overall, differences in neuroinflammation and Sirt1 interactions with chromatin distinguished shorter- and longer-lived animals, suggesting the importance of preserving microglia and Sirt1 functional efficiency for longevity.
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影响因子：
30.8
作者：
Guarente, L
通讯作者：
Guarente, L
Sirt1-Sirt3 轴调节人血脑屏障通透性以应对缺血
影响因子：
11.4
作者：
Chen T;Dai SH;Li X;Luo P;Zhu J;Wang YH;Fei Z;Jiang XF
通讯作者：
Jiang XF
影响因子：
29
作者：
Camacho-Pereira J;Tarragó MG;Chini CCS;Nin V;Escande C;Warner GM;Puranik AS;Schoon RA;Reid JM;Galina A;Chini EN
通讯作者：
Chini EN
影响因子：
10.9
作者：
Canto, Caries;Auwerx, Johan
通讯作者：
Auwerx, Johan
影响因子：
4.8
作者：
Bitterman, KJ;Anderson, RM;Sinclair, DA
通讯作者：
Sinclair, DA