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Research into the cause of functional decline that may occur with aging has been progressing rapidly in recent years. Researchers in the field of aging and longevity research are working to develop treatments that not only delay the onset of age-related diseases but may actually reverse some aspects of them. A new study evaluates one nutritional strategy that may boost cellular defenses in older individuals to protect against oxidative stress, correct mitochondrial defects, increase muscle strength and cognition, and promote healthy aging.

A March 2021 pilot human clinical trial published in Clinical and Translational Medicine suggests that older individuals taking GlyNAC—a combination of glycine and N-acetylcysteine that are precursors of the antioxidant glutathione—may improve some causative factors associated with aging, including glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, body fat, genomic toxicity, muscle strength, gait speed, exercise capacity, and cognitive function.¹ Authors of the study indicate that GlyNAC supplementation could be a simple, safe, and effective nutritional strategy for older individuals.¹

This exploratory pilot open-label clinical trial tested the effects of nutritional supplementation with GlyNAC for a 24-week period and GlyNAC withdrawal for 12 weeks.² Researchers worked with older adults, age 70-80 years, and compared them with gender-matched younger adults between 21 and 30 years old. They saw improvements in many characteristic defects of aging, and specifically, after taking GlyNAC for 24 weeks, all of the defects in older adults improved and some even reversed to the levels found in young adults. The benefits declined after stopping supplementation for 12 weeks.²

“It is believed that correcting these aging hallmarks could improve or reverse many age-related disorders and help people age in a healthier way,” said corresponding author endocrinologist Dr. Rajagopal Sekhar in a press release issued by Baylor College of Medicine. “However, we do not fully understand why these hallmark defects happen, and there are currently no solutions to fix even a single hallmark defect in aging.”² Dr. Sekhar, who has been studying natural aging in older humans for the last 20 years, believes that improving the health of malfunctioning mitochondria in aging is the key to a healthier lifespan.^2,3 Some studies suggest that glutathione levels in older people may be lower than those in younger people,^1,4 and the levels of oxidative stress may be much higher.^2,5,6

Researchers discovered that the primary reason for glutathione deficiency in older adults may be diminished synthesis caused by decreased availability of glycine and cystine.¹ This is why they believe GlyNAC is an improvement over supplementation with NAC alone. Glutathione synthesis requires two biochemical steps—in the first step, cysteine is added to glutamic acid to form the intermediate glutamylcysteine, and in the second step, glycine is added to glutamylcysteine to form glutathione.¹ The study’s authors speculate that GlyNAC represents three forces that could be operating simultaneously to result in widespread improvements in older adults:

• The correction of glutathione deficiency results in correction of oxidative stress and mitochondrial dysfunction.
• GlyNAC contains glycine, an important methyl-group donor that is important for normal brain function.
• GlyNAC contains N-acetylcysteine, which functions as a cysteine donor and is crucially important in energy metabolism.¹

Researchers said they call this the “power of 3” because they believe it takes the combined benefits of glycine, NAC, and glutathione to reach this widespread improvement in older individuals.²

Breakthroughs in aging research have begun revolutionizing the way we think about biology, and recent discoveries have brought us closer to the development of therapies that will not only extend the lifespan but also improve quality of life as we age. For further reading on the topic of aging, please consider the following IFM-authored materials:

Immune Aging & Therapeutic Targets

Slowing Neurodegeneration With Exercise

Nathan Price, PhD, on Predictive Biomarkers and Biological Aging

References

1. Kumar P, Liu C, Hsu JW, et al. Glycine and N?acetylcysteine (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. Clin Transl Med. 2021;11(3):e372. doi:10.1002/ctm2.372
2. Shalchi H. GlyNAC improves strength and cognition in older humans. Baylor College of Medicine. Published March 29, 2021. Accessed April 8, 2021. https://www.bcm.edu/news/glynac-improves-strength-and-cognition-in-older-humans
3. Espinoza SE, Guo H, Fedarko N, et al. Glutathione peroxidase enzyme activity in aging. J Gerontol A Biol Sci Med Sci. 2008;63(5):505-509. doi:10.1093/gerona/63.5.505
4. Lang CA, Naryshkin S, Schneider DL, Mills BJ, Lindeman RD. Low blood glutathione levels in healthy aging adults. J Lab Clin Med. 1992;120(5):720-725. doi:10.5555/uri:pii:002221439290079Z
5. Maher P. The effects of stress and aging on glutathione metabolism. Ageing Res Rev. 2005;4(2):288-314. doi:10.1016/j.arr.2005.02.005
6. Venkateshappa C, Harish G, Mahadevan A, Srinivas Bharath MM, Shankar SK. Elevated oxidative stress and decreased antioxidant function in the human hippocampus and frontal cortex with increasing age: implications for neurodegeneration in Alzheimer’s disease. Neurochem Res. 2012;37(8):1601-1614. doi:10.1007/s11064-012-0755-8