The population of older adults is expected to exceed 2.1 billion by 2050, according to the World Health Organization. This predicted increase in the older human population will increase the need for healthcare and will intensify the stress on healthcare systems around the world. To understand what causes unhealthy aging, scientific research has identified nine aging hallmarks that represent specific defects that are believed to contribute to health decline while aging.
“It is believed that correcting aging hallmarks could help people age in a healthier way,” said corresponding author Dr. Rajagopal Sekhar, professor of medicine – endocrinology, diabetes and metabolism at Baylor College of Medicine. “However, we do not fully understand why these aging hallmarks occur in the first place, and therefore there have been no proven solutions via human randomized clinical trials to improve or correct aging hallmarks in aging humans. Until now.”
For the last 20 years, Sekhar has been studying natural aging in humans and animal models to understand why age-related declines occur and how to correct them. His work brings mitochondria, known as the batteries of the cell, as well as free radicals and glutathione – the body’s main antioxidant – to discussions that could explain why we age and how to improve health while aging.
The first randomized clinical trial of GlyNAC
“This is the first randomized clinical trial of GlyNAC supplementation in older humans, and it found that a wide variety of age-associated abnormalities, including notable hallmarks of aging, improved in older adults supplemented with GlyNAC, while no improvements were seen in those receiving placebo,” Sekhar said.
The improvements includes oxidative stress, glutathione deficiency and multiple aging hallmarks affecting mitochondrial dysfunction, mitophagy, inflammation, insulin resistance, endothelial dysfunction, genomic damage, stem cell fatigue and cellular senescence. These were associated with improvements in muscle strength, gait speed, exercise capacity, waist circumference and blood pressure.
The improvements in oxidative stress, glutathione levels and mitochondrial function in the muscle tissue of older humans taking GlyNAC were similar to the improvements in organs such as the heart, liver and kidneys of aged mice supplemented with GlyNAC as reported in the researchers’ recent publication. Taken together, the results of these studies show that GlyNAC supplementation can improve these defects in many different organs of the body.
“GlyNAC supplementation in aging mice increased their length of life by 24%,” said Sekhar. “Gait speed is reported to be associated with survival in older humans. Our randomized clinical trial found a significant improvement in gait speed in older adults supplemented with GlyNAC. This raises the interesting question of whether GlyNAC supplementation could have implications for survival in people.”
In addition, GlyNAC supplementation improved muscle strength in the upper and lower extremity and a trend toward increased exercise capacity.
“These findings could have additional implications for improving the health of older humans, especially in terms of being able to be more physically active,” said Sekhar.
Mitochondria dysfunction, oxidative stress and aging
Mitochondria generate energy needed for supporting cellular functions; therefore, normal mitochondrial function is critically important for a healthy life. Sekhar believes that improving the health of malfunctioning mitochondria in aging is the key to healthy aging.
The ability of mitochondria to work well declines as we age. Sekhar’s group discovered earlier that supplementing GlyNAC in aged mice corrected malfunctioning mitochondria. However, to definitively determine whether GlyNAC supplementation benefited people, a placebo-controlled randomized human clinical trial was required.
The team’s randomized clinical trial found that older people have widespread mitochondrial damage and other age-associated defects compared to young people. After 16-weeks of GlyNAC supplementation, mitochondrial function of older people improve toward levels found in young people. This was accompanied by improvements in multiple additional outcomes as reported in the publication.
Analysis of the molecular data from the trial suggests that the GlyNAC supplementation is able to fill cells with younger and more efficient mitochondria,” Sekhar said.
A second vital benefit offered by supplementing GlyNAC is that it also helps protect the body from an important problem called oxidative stress. Oxidative stress is caused by high levels of toxic waste products known as reactive oxygen species or free-radicals. Oxidative stress can damage our cells, membranes, lipids, proteins and DNA, and is very common in aging.
Glutathione is a natural antioxidant that cells make every day. Glutathione works by protecting cells from harmful oxidative stress. However, in older people, not only are glutathione levels very low but the harmful oxidative stress is very high.
GlyNAC supplementation corrects glutathione deficiency and lowers oxidative stress in older humans back to youthful levels.
Taking GlyNAC is not the same as taking glutathione: Introducing the ‘Power of 3’
“It is really important to understand that this trial supplemented GlyNAC, and did not supplement glutathione,” says Sekhar. “This is because our body does not get its glutathione from food, but has to make its own glutathione every day. All our organs maintain different levels of glutathione in a delicate balance that favors health. Too little glutathione cannot fight the harmful oxidative stress, and too much glutathione could lead to harmful reductive stress,” said Sekhar. “This is why GlyNAC is a natural solution for correcting glutathione deficiency, because it provides the raw materials to help cells to make their own glutathione in just the right amount. We have seen this repeatedly in all our prior studies supplementing GlyNAC, including this trial.”
“Glycine and cysteine (from ‘NAC’ in GlyNAC) have health benefits on their own. We believe that the health improvements we saw in this trial are due to the combined effort of three separate components – glycine, cysteine and glutathione – and not just due to glutathione itself,” Sekhar said. “We refer to this combination as the ‘Power of 3.”
“This study was effort intensive and took many years to complete. I take this opportunity to thank all my co-investigators, nursing staff, and everyone who helped with this trial. I especially thank all the trial participants who volunteered to participate in this research,” Sekhar said.
Sekhar led the study team consisting of Premranjan Kumar, Chun Liu, James Suliburk, Jean W. Hsu, Raja Muthupillai, Farook Jahoor, Charles G. Minard and George E. Taffet, all at Baylor College of Medicine. For this trial, Sekhar received funding support from the National Institutes of Health/National Institute of Aging, and philanthropic support from the McNair Medical Institute at the Robert and Janice McNair Foundation in Houston, TX.
Baylor College of Medicine holds a patent on GlyNAC, which has been licensed to Nestlé Health Science. GlyNAC is marketed in the United States by Nestlé Health Science under the name CelltrientTM Cellular Protect. Nestlé Health Science did not provide financial or material support for this research work.
As he moves forward, Sekhar plans to expand on his work to understand more about the health benefits of GlyNAC supplementation on cells, tissues and organs of the body. Additionally, as reported in their previously published exploratory study, Sekhar’s group found that GlyNAC supplementation in older humans could improve memory and cognition. He has studied this further in aged mice and found that GlyNAC supplementation appears to correct multiple age-related declines directly in the brain, and was associated with improvements in memory and brain health – a report on these emerging new and exciting findings is in development.