Hexosamine pathway activation improves memory but does not extend lifespan in mice.
Hexosamine pathway activation improves memory but does not extend lifespan in mice.
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作者：
葡萄糖胺喂养和己糖胺生物合成途径（HBP）的遗传激活与改善蛋白质质量控制和延长寿命有关。然而，作为一种能量传感器，HBP与肿瘤进展和糖尿病有关。考虑到这些相反的结果，探索哺乳动物慢性HBP激活的长期影响势在必行。因此，我们询问HBP激活是否影响小鼠的代谢、协调、记忆和存活。在饮用水中补充N-乙酰-D-葡萄糖胺（GlcNAc）对男性体重没有不良影响，但会增加年轻女性的体重。葡萄糖或胰岛素耐量在20个月大之前不受影响。值得注意的是，我们观察到补充有GlcNAc的年轻雄性小鼠的记忆改善。GlcNAc治疗未改变存活率。为了评估遗传HBP激活的影响，我们在所有小鼠组织中过表达该途径的关键酶GFAT 1和组成型激活突变体形式。我们在小鼠大脑中检测到HBP产物UDP‐GlcNAc水平升高，但没有发现对行为，记忆或生存的任何影响。总之，虽然饮食GlcNAc补充剂没有延长小鼠的生存期，但它对记忆有积极影响，并且通常耐受良好。己糖胺生物合成途径（HBP）的激活与改善蛋白质质量控制和延长寿命有关。然而，作为一种能量传感器，HBP与肿瘤进展和糖尿病有关。使用慢性HBP激活和终身观察，我们发现补充GlcNAc的年轻雄性小鼠的存活率没有影响，但记忆功能增强。
Glucosamine feeding and genetic activation of the hexosamine biosynthetic pathway (HBP) have been linked to improved protein quality control and lifespan extension. However, as an energy sensor, the HBP has been implicated in tumor progression and diabetes. Given these opposing outcomes, it is imperative to explore the long‐term effects of chronic HBP activation in mammals. Thus, we asked if HBP activation affects metabolism, coordination, memory, and survival in mice. N‐acetyl‐D‐glucosamine (GlcNAc) supplementation in the drinking water had no adverse effect on weight in males but increased weight in young females. Glucose or insulin tolerance was not affected up to 20 months of age. Of note, we observed improved memory in young male mice supplemented with GlcNAc. Survival was not changed by GlcNAc treatment. To assess the effects of genetic HBP activation, we overexpressed the pathway's key enzyme GFAT1 and a constitutively activated mutant form in all mouse tissues. We detected elevated levels of the HBP product UDP‐GlcNAc in mouse brains, but did not find any effects on behavior, memory, or survival. Together, while dietary GlcNAc supplementation did not extend survival in mice, it positively affected memory and is generally well tolerated. The activation of the hexosamine biosynthetic pathway (HBP) is linked to improved protein quality control and lifespan extension. However, as an energy sensor, the HBP has been implicated in tumor progression and diabetes. Using chronic HBP activation and lifelong observation, we find no effect on survival but enhanced memory function in young male mice supplemented with GlcNAc.
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影响因子：
16.6
作者：
Ruegenberg S;Mayr FAMC;Atanassov I;Baumann U;Denzel MS
通讯作者：
Denzel MS
影响因子：
4.5
作者：
Na J;Musselman LP;Pendse J;Baranski TJ;Bodmer R;Ocorr K;Cagan R
通讯作者：
Cagan R
影响因子：
4.6
作者：
Ryczko MC;Pawling J;Chen R;Abdel Rahman AM;Yau K;Copeland JK;Zhang C;Surendra A;Guttman DS;Figeys D;Dennis JW
通讯作者：
Dennis JW
影响因子：
6.1
作者：
Dalirfardouei, Razieh;Karimi, Gholamreza;Jamialahmadi, Khadijeh
通讯作者：
Jamialahmadi, Khadijeh
影响因子：
7.5
作者：
Denzel, Martin S.;Antebi, Adam
通讯作者：
Antebi, Adam