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Supplementation with Brush Border Enzyme Alkaline Phosphatase Slows Aging.
Rejuvenation Research ( IF 2.2 ) Pub Date : 2020-04-17 , DOI: 10.1089/rej.2020.2335
James W Larrick 1, 2 , Andrew R Mendelsohn 1, 2
Affiliation  

Diminished integrity of the intestinal epithelial barrier with advanced age is believed to contribute to aging-associated dysfunction and pathologies in animals. In mammals, diminished gut integrity contributes to inflammaging, the increase in inflammatory processes observed in old age. Recent work suggests that expression of intestinal alkaline phosphatase (IAP) plays a key role in maintaining gut integrity. IAP expression decreases with increasing age in mice and humans. Absence of IAP leads to liver inflammation and shortened life-spans in mice lacking the IAP gene. In normal mice, exogenous supplemental IAP reverses age-induced barrier dysfunction, improves aging-associated metabolic dysfunction, prevents microbiome dysbiosis (imbalance), and extends life-span. Consistent with IAP playing a conserved role in maintaining gut integrity, increased dietary IAP increases aging-diminished physical performance in flies. IAP helps maintain gut integrity in part by supporting the expression of tight junction proteins that maintain the intestinal epithelial barrier and by inactivating bacterial pro-inflammatory factors such as lipopolysaccharides (LPS) by dephosphorylation. Recombinant IAP is in late clinical trials for sepsis-associated acute kidney injury, suggesting it may soon become available as a therapeutic. Taken together, these reports support the idea that directly increasing IAP levels by supplemental recombinant IAP or by indirectly increasing IAP levels using dietary means to induce endogenous IAP may slow the development of aging-associated pathologies.

中文翻译:

补充刷状边界酶碱性磷酸酶可延缓衰老。

随着年龄的增长,肠道上皮屏障的完整性降低被认为是导致动物衰老相关功能障碍和病理的原因。在哺乳动物中,肠道完整性下降会导致发炎,这是老年期发炎过程的增加。最近的工作表明,肠碱性磷酸酶(IAP)的表达在维持肠道完整性方面起着关键作用。在小鼠和人类中,IAP表达随着年龄的增长而降低。缺乏IAP会导致肝脏炎症,并缩短缺乏IAP基因的小鼠的寿命。在正常小鼠中,外源补充IAP可逆转年龄引起的屏障功能障碍,改善衰老相关的代谢功能障碍,防止微生物组营养不良(失衡),并延长寿命。与IAP在维持肠道完整性方面起着保守的作用一致,饮食中IAP的增加会增加果蝇衰老的身体机能。IAP通过支持维持肠上皮屏障的紧密连接蛋白的表达以及通过去磷酸化灭活细菌促炎因子(例如脂多糖)来帮助维持肠道完整性。重组IAP在败血症相关的急性肾损伤的后期临床试验中,表明它可能很快就可以用作治疗药物。综上所述,这些报告支持这样的想法,即通过补充重组IAP直接增加IAP水平或通过使用饮食手段诱导内源性IAP间接增加IAP水平可能减缓与衰老相关的疾病的发展。IAP通过支持维持肠上皮屏障的紧密连接蛋白的表达以及通过去磷酸化来灭活细菌促炎因子(例如脂多糖)来帮助维持肠道完整性。重组IAP在败血症相关的急性肾损伤的后期临床试验中,表明它可能很快会成为一种治疗方法。综上所述,这些报告支持这样的想法,即通过补充重组IAP直接增加IAP水平或通过使用饮食手段诱导内源性IAP间接增加IAP水平可能减缓与衰老相关的疾病的发展。IAP通过支持维持肠上皮屏障的紧密连接蛋白的表达以及通过去磷酸化来灭活细菌促炎因子(例如脂多糖)来帮助维持肠道完整性。重组IAP在败血症相关的急性肾损伤的后期临床试验中,表明它可能很快就可以用作治疗药物。综上所述,这些报告支持这样的想法,即通过补充重组IAP直接增加IAP水平或通过使用饮食手段诱导内源性IAP间接增加IAP水平可能减缓与衰老相关的疾病的发展。重组IAP在败血症相关的急性肾损伤的后期临床试验中,表明它可能很快就可以用作治疗药物。综上所述,这些报告支持这样的想法,即通过补充重组IAP直接增加IAP水平或通过使用饮食手段诱导内源性IAP间接增加IAP水平可能减缓与衰老相关的疾病的发展。重组IAP在败血症相关的急性肾损伤的后期临床试验中,表明它可能很快就可以用作治疗药物。综上所述,这些报告支持这样的想法,即通过补充重组IAP直接增加IAP水平或通过使用饮食手段诱导内源性IAP间接增加IAP水平可能减缓与衰老相关的疾病的发展。
更新日期:2020-04-17
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