==== Front Innov Aging Innov Aging innovateage Innovation in Aging 2399-5300 Oxford University Press US 10.1093/geroni/igaa057.3157 igaa057.3157 Abstracts Session 7715 (Symposium) AcademicSubjects/SOC02600 Reversing cognitive-decline in older adults in an open-label clinical trial: novel mechanisms and the role of GlyNAC Liu Chun Sekhar Rajagopal Kumar Premranjan Minard Charles Chacko Shaji Baylor College of Medicine, Houston, Texas, United States 2020 16 12 2020 16 12 2020 4 Suppl 1 Program Abstracts from The GSA 2020 Annual Scientific Meeting “Turning 75: Why Age Matters”857 857 © The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America.2020This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Abstract Age-associated cognitive-decline is an important risk factor for Alzheimer’s disease, but interventions are lacking. We conducted an open-label trial to test our hypotheses on whether: (1) compared to 8 healthy young adults (25y), 8 ‘healthy’ older adults (74y) have cognitive decline, decreased glucose availability for the brain due to mitochondrial dysfunction, elevated insulin-resistance, oxidative-stress and elevated inflammation; (2) supplementing glycine and N-acetylcysteine (GlyNAC) for 24-weeks corrects deficiency of the endogenous-antioxidant Glutathione and improves these defects, and thereby cognition; (3) stopping GlyNAC supplementation for 12-weeks results in a decline in accrued benefits. Outcome measures included cognitive testing (Montreal cognitive assessment; trail-making tests; verbal-fluency tests; digital-symbol substitution-test), mitochondrial fuel-oxidation, RBC-Glutathione concentrations, plasma oxidative-stress, insulin-resistance and inflammation, and tracer-studies to measure glucose metabolism. Results validated our hypotheses and showed that GlyNAC-supplementation corrected these defects and improved cognition. This trial suggests that supplementing GlyNAC may be important for improving/preventing age-associated cognitive-decline in older adults.