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

被引:26
作者
Kumar, Premranjan [1 ]
Liu, Chun [1 ]
Suliburk, James W. [2 ]
Minard, Charles G. [3 ]
Muthupillai, Raja [4 ]
Chacko, Shaji [5 ]
Hsu, Jean W. [5 ]
Jahoor, Farook [5 ]
Sekhar, Rajagopal, V [1 ,6 ]
机构
[1] Baylor Coll Med, Dept Med, Div Endocrinol Diabet & Metab, Translat Metab Unit, One Baylor Plaza, Houston, TX 77030 USA
[2] Baylor Coll Med, Dept Surg, One Baylor Plaza, Houston, TX 77030 USA
[3] Baylor Coll Med, Inst Clin & Translat Res, One Baylor Plaza, Houston, TX 77030 USA
[4] Baylor St Lukes Med Ctr, Houston, TX 77030 USA
[5] Baylor Coll Med, USDA ARS Childrens Nutr Res Ctr, Houston, TX 77030 USA
[6] Harris Hlth, Thomas St HIV Hlth Ctr, Houston, TX 77009 USA
关键词
premature aging; HIV; mitochondrial function; oxidative stress; GlyNAC; Glutathione; cognition; physical function; FATTY-ACID OXIDATION; INCREASING GLUTATHIONE; ANTIRETROVIRAL THERAPY; DNA-DAMAGE; GAIT SPEED; MECHANISMS; MORTALITY; CYSTEINE;
D O I
10.3390/biomedicines8100390
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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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页码:1 / 22
页数:22
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