A study led by the University of New South Wales has revealed that some symptoms of aging could be reversed by replenishing two molecules that occur naturally in the body. The discovery could help improve physical performance in older adults.
The two molecules can be boosted to reverse an age-related decline of blood flow to tissues and organs. This restoration process successfully increased exercise capacity and physical endurance in mice.
The research has demonstrated, for the first time, that the body’s capacity for exercise decreases as levels of the metabolite NAD+ decline.
When mice were treated with the NAD+ booster NMN and increasing levels of hydrogen sulphide (H2S), physical endurance was improved by over 60 percent in both young and old mice.
The study revealed that endothelial cells, the cells that line the blood vessels, are the primary driver of aging and are most likely the reason that older people feel like they have less energy.
“We become weaker and less fit after 50, and eventually succumb to diseases of aging,” said senior author Dr. David Sinclair. “Remarkably, by feeding mice NMN and H2S it restores NAD+ levels in endothelial cells and makes them believe they are young and exercised.”
“With exercise, the effect is even more dramatic. We saw 32-month-old mice, roughly equivalent to a 90-year-old human – receiving the combination of molecules for four weeks ran, on average, twice as far as untreated mice. Mice treated only with NMN alone ran 1.6 times further than untreated mice.”
The researchers found that the protein SIRT1 was stimulated in the mice, which led to the restoration of capillary formation in muscle.
“Age plays a critical role in the links between blood vessels and muscle, and points to a loss of NAD+ and SIRT1 as the reason people lose the capacity to exercise as they age,” said lead author Dr. Abhirup Das.
“It has significant impact on frailty because one of the main reasons for frailty is reduced blood flow that affects every part of our body. And reduced muscle function makes us weak. Our bodies already make NAD+ in our cells, but after 50 its levels drop dramatically.”
“Exercise is a way to prevent decline in blood flow but these findings show that by restoring the levels of NAD+ in mice equivalent to 60 year old humans, we can get the same benefits of exercise.”
Dr. Sinclair and Dr. Lindsay Wu have been working for five years to make NAD+ boosters into therapeutic agents. The ultimate goal is the development of NMN-based drugs that replicate the benefits of exercise by increasing blood flow and oxygenation of muscles.
“This new study adds to the body of work showing that the restoration of NAD in mammals can delay and reverse many of the effects of aging. NAD+ boosters, particularly when combined with H2S, are some of the most promising molecules in medical research today,” said Dr. Sinclair.
The research could ultimately lead to improved mobility in older adults, better athletic ability, and could help to reduce the risk of age-related diseases like dementia, liver failure, and stroke.
“If these findings translate from mouse to human, we could have a revolutionary impact on the quality of life of older people,and not to mention the benefits of avoiding diseases of aging,” said Dr. Wu.
The study is published in the journal Cell.