Translational Metabolism Unit, Section of Endocrinology, Diabetes and Metabolism, Department of Medicine.
Baylor College of Medicine, Houston, TX, USA.
J Gerontol A Biol Sci Med Sci. 2023 Jan 26;78(1):75-89. doi: 10.1093/gerona/glac135.
Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial.
Twenty-four OA and 12 young adults (YA) were studied. OA was randomized to receive either GlyNAC (N = 12) or isonitrogenous alanine placebo (N = 12) for 16-weeks; YA (N = 12) received GlyNAC for 2-weeks. Participants were studied before, after 2-weeks, and after 16-weeks of supplementation to assess GSH concentrations, OxS, MFO, molecular regulators of energy metabolism, inflammation, endothelial function, IR, aging hallmarks, gait speed, muscle strength, 6-minute walk test, body composition, and blood pressure.
Compared to YA, OA had GSH deficiency, OxS, mitochondrial dysfunction (with defective molecular regulation), inflammation, endothelial dysfunction, IR, multiple aging hallmarks, impaired physical function, increased waist circumference, and systolic blood pressure. GlyNAC (and not placebo) supplementation in OA improved/corrected these defects.
GlyNAC supplementation in OA for 16-weeks was safe and well-tolerated. By combining the benefits of glycine, NAC and GSH, GlyNAC is an effective nutritional supplement that improves and reverses multiple age-associated abnormalities to promote health in aging humans. Clinical Trials Registration Number: NCT01870193.
氧化应激（OxS）升高、线粒体功能障碍和衰老特征被认为是导致衰老的关键因素，但改善/逆转老年人（OA）中的这些缺陷具有挑战性。在之前的研究中，我们发现细胞内抗氧化剂谷胱甘肽（GSH）的缺乏可能起作用，并报告说在年老的小鼠中补充 GlyNAC（甘氨酸和 N-乙酰半胱氨酸[NAC]的组合）可改善 GSH 缺乏、OxS、线粒体脂肪酸氧化（MFO）和胰岛素抵抗（IR）。为了测试 GlyNAC 补充剂是否可改善 OA 中的 GSH 缺乏、OxS、线粒体功能障碍、IR、身体功能和衰老特征，我们进行了一项安慰剂对照随机临床试验。
共研究了 24 名 OA 和 12 名年轻成年人（YA）。OA 随机分为接受 GlyNAC（N = 12）或等氮丙氨酸安慰剂（N = 12）治疗 16 周；YA（N = 12）接受 GlyNAC 治疗 2 周。参与者在补充前、补充 2 周后和补充 16 周后接受研究，以评估 GSH 浓度、OxS、MFO、能量代谢的分子调节剂、炎症、内皮功能、IR、衰老特征、步态速度、肌肉力量、6 分钟步行测试、身体成分和血压。
与 YA 相比，OA 存在 GSH 缺乏、OxS、线粒体功能障碍（分子调节缺陷）、炎症、内皮功能障碍、IR、多种衰老特征、身体功能受损、腰围增加和收缩压升高。GlyNAC（而非安慰剂）补充 OA 可改善/纠正这些缺陷。
OA 接受 16 周 GlyNAC 补充是安全且耐受良好的。通过结合甘氨酸、NAC 和 GSH 的益处，GlyNAC 是一种有效的营养补充剂，可改善和逆转与年龄相关的多种异常，从而促进人类健康衰老。临床试验注册号：NCT01870193。
