{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:16:02Z","timestamp":1791951362304,"version":"4.3.4"},"reference-count":80,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,3,27]],"date-time":"2021-03-27T00:00:00Z","timestamp":1616803200000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Oxidative stress (OxS) and mitochondrial dysfunction are implicated as causative factors for aging. Older adults (OAs) have an increased prevalence of elevated OxS, impaired mitochondrial fuel\u2010oxidation (MFO), elevated inflammation, endothelial dysfunction, insulin resistance, cognitive decline, muscle weakness, and sarcopenia, but contributing mechanisms are unknown, and interventions are limited\/lacking. We previously reported that inducing deficiency of the antioxidant tripeptide glutathione (GSH) in young mice results in mitochondrial dysfunction, and that supplementing GlyNAC (combination of glycine and N\u2010acetylcysteine [NAC]) in aged mice improves naturally\u2010occurring GSH deficiency, mitochondrial impairment, OxS, and insulin resistance. This pilot trial in OA was conducted to test the effect of GlyNAC supplementation and withdrawal on intracellular GSH concentrations, OxS, MFO, inflammation, endothelial function, genotoxicity, muscle and glucose metabolism, body composition, strength, and cognition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A 36\u2010week open\u2010label clinical trial was conducted in eight OAs and eight young adults (YAs). After all the participants underwent an initial (pre\u2010supplementation) study, the YAs were released from the study. OAs were studied again after GlyNAC supplementation for 24 weeks, and GlyNAC withdrawal for 12 weeks. Measurements included red\u2010blood cell (RBC) GSH, MFO; plasma biomarkers of OxS, inflammation, endothelial function, glucose, and insulin; gait\u2010speed, grip\u2010strength, 6\u2010min walk test; cognitive tests; genomic\u2010damage; glucose\u2010production and muscle\u2010protein breakdown rates; and body\u2010composition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>GlyNAC supplementation for 24 weeks in OA corrected RBC\u2010GSH deficiency, OxS, and mitochondrial dysfunction; and improved inflammation, endothelial dysfunction, insulin\u2010resistance, genomic\u2010damage, cognition, strength, gait\u2010speed, and exercise capacity; and lowered body\u2010fat and waist\u2010circumference. However, benefits declined after stopping GlyNAC supplementation for 12 weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>GlyNAC supplementation for 24\u2010weeks in OA was well tolerated and lowered OxS, corrected intracellular GSH deficiency and mitochondrial dysfunction, decreased inflammation, insulin\u2010resistance and endothelial dysfunction, and genomic\u2010damage, and improved strength, gait\u2010speed, cognition, and body composition. Supplementing GlyNAC in aging humans could be a simple and viable method to promote health and warrants additional investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.372","type":"journal-article","created":{"date-parts":[[2021,3,27]],"date-time":"2021-03-27T05:37:31Z","timestamp":1616823451000},"source":"Crossref","is-referenced-by-count":174,"title":["Glycine and N\u2010acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial"],"prefix":"10.1002","volume":"11","author":[{"given":"Premranjan","family":"Kumar","sequence":"first","affiliation":[{"name":"Translational Metabolism Unit, Division of Endocrinology, Diabetes and Metabolism Department of Medicine, Baylor College of Medicine  Houston Texas 77030 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