Supplementing Glycine and N-acetylcysteine (GlyNAC) in Aging HIV Patients Improves Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Endothelial Dysfunction, Insulin Resistance, Genotoxicity, Strength, and Cognition: Results of an Open-Label Clinical Trial.
Supplementing Glycine and N-acetylcysteine (GlyNAC) in Aging HIV Patients Improves Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Endothelial Dysfunction, Insulin Resistance, Genotoxicity, Strength, and Cognition: Results of an Open-Label Clinical Trial.
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在老年HIV患者中补充甘氨酸和N-乙酰半胱氨酸(GlyNAC)可改善氧化应激、线粒体功能障碍、炎症、内皮功能障碍、胰岛素抵抗、遗传毒性、强度和认知：开放标签临床试验的结果。
DOI：
10.3390/biomedicines8100390
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发表时间：
2020-09-30
期刊：
影响因子：
4.7
通讯作者：
Sekhar RV
中科院分区：
文献类型：
--
作者：
Kumar P;Liu C;Suliburk JW;Minard CG;Muthupillai R;Chacko S;Hsu JW;Jahoor F;Sekhar RV
背景：HIV（PWH）患者会出现老年合并症，包括在较年轻时出现功能和认知下降。然而，促成机制不明确，也缺乏干预措施。我们假设，抗氧化蛋白谷胱甘肽（GSH）的缺乏导致PWH中代表过早衰老的多种缺陷，并且这些缺陷可以通过补充GSH前体甘氨酸和N-乙酰半胱氨酸（GlyNAC）来改善。方法：我们进行了一项开放标签的临床试验，在基线时研究了8名PWH和8名匹配的未感染对照。在接受GlyNAC后12周和停止GlyNAC后8周再次研究PWH。对照组未接受补充。结果指标包括红细胞和肌肉GSH浓度、线粒体功能、线粒体自噬和自噬、氧化应激、炎症、内皮功能、基因组损伤、胰岛素抵抗、葡萄糖生成、肌肉蛋白分解率、身体组成、身体功能和认知。结果：PWH在测量结果方面存在显著缺陷，补充GlyNAC后改善。然而，停止GlyNAC后，益处消退。结论：这项开放标签试验发现PWH具有基于多种生物和功能缺陷的过早衰老，并确定了认知和身体衰退的新机制解释。GlyNAC的营养补充可改善PWH中提示过早衰老的合并症，包括功能和认知下降，并需要进行额外的研究。
Background: Patients with HIV (PWH) develop geriatric comorbidities, including functional and cognitive decline at a younger age. However, contributing mechanisms are unclear and interventions are lacking. We hypothesized that deficiency of the antioxidant protein glutathione (GSH) contributes to multiple defects representing premature aging in PWH, and that these defects could be improved by supplementing the GSH precursors glycine and N-acetylcysteine (GlyNAC). Methods: We conducted an open label clinical trial where eight PWH and eight matched uninfected-controls were studied at baseline. PWH were studied again 12-weeks after receiving GlyNAC, and 8-weeks after stopping GlyNAC. Controls did not receive supplementation. Outcome measures included red-blood cell and muscle GSH concentrations, mitochondrial function, mitophagy and autophagy, oxidative stress, inflammation, endothelial function, genomic damage, insulin resistance, glucose production, muscle-protein breakdown rates, body composition, physical function and cognition. Results: PWH had significant defects in measured outcomes, which improved with GlyNAC supplementation. However, benefits receded after stopping GlyNAC. Conclusions: This open label trial finds that PWH have premature aging based on multiple biological and functional defects, and identifies novel mechanistic explanations for cognitive and physical decline. Nutritional supplementation with GlyNAC improves comorbidities suggestive of premature aging in PWH including functional and cognitive decline, and warrants additional investigation.
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影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
影响因子：
11.8
作者：
Guaraldi, Giovanni;Orlando, Gabriella;Palella, Frank
通讯作者：
Palella, Frank
影响因子：
3.3
作者：
Chacko, Shaji K.;Sunehag, Agneta L.;Haymond, Morey W.
通讯作者：
Haymond, Morey W.
DOI：
10.1097/00126334-200306012-00003
发表时间：
2003-06-01
影响因子：
3.6
作者：
Mack, KA;Ory, MG
通讯作者：
Ory, MG
DOI：
10.1111/j.1532-5415.1972.tb00787.x
发表时间：
1972-01-01
影响因子：
6.3
作者：
HARMAN, D
通讯作者：
HARMAN, D