Mitochondria and the nucleus can't communicate properly due to a lack of NAD+; this promotes aging. However, mitochondrial dysfunction can be prevented or reversed with NAD+ supplementation, which restores communication and reverses symptoms of aging.
The cell is a complicated machine that requires the cooperation and communication of numerous components, especially between the command center and the powerhouse - the nucleus and mitochondria. In mice, researchers at Harvard University discovered in 2013 that the disconnection of nuclear-mitochondrial communication causes accelerated aging. On the bright side, it may be reversed by a natural substance produced by the body called nicotinamide adenine dinucleotide (NAD+).
“The aging process we discovered is like a married couple — when they are young, they communicate well, but over time, living in close quarters for many years, communication breaks down,” said senior author of the study, David Sinclair of Harvard Medical School in a statement. “And just like with a couple, restoring communication solved the problem.”
Mitochondria are tiny parts inside complicated cells that generate adenosine triphosphate (ATP), the body's energy source. Mitochondria originated from bacteria that integrated themselves into host cells and specialized in energy production about 2 billion years ago. Mitochondria retain a small amount of their own DNA and continue to play an important role in cellular metabolism, despite being isolated for millions of years. Scientists have identified mitochondrial dysfunction as one of the indicators of aging, which leads to age-related illnesses such as cancer, diabetes, and Alzheimer's disease.
Aging is associated with a progressive deterioration in mitochondrial function, according to researchers. However, while the number of nuclear proteins remained constant in older mice, those encoded by mitochondrial DNA were significantly decreased, according to the researchers.
It was discovered that the decreased levels of NAD+ molecules might be one of the underlying causes. The fundamental molecule acts as a shuttle bus, transporting information between the nucleus and mitochondria. However, as we age, NAD+ levels fall for reasons that scientists are still unclear.
According to the research, NAD+ is vital for SIRT1, a protein that protects the nuclear-mitochondrial communication from an interfering molecule — HIF-1. Without SIRT1 to monitor HIF-1, it goes rogue and wreaks havoc on the conversation. The study discovered that this disruption lowers energy production in cells and speeds up the aging process. The fact that this is the first time nuclear-mitochondrial communication during aging has been documented, as well as the finding that it is "reversible."
They discovered that by giving 2-year-olds NAD+ injections, they could restore mitochondrial function and repair the cross-genome communication network. One week of therapy was enough to bring biochemical indicators of muscular health to those seen in 6-month-old mice. It would be like turning a 60-year-old human into a 20-year-old in specific sections.
Nicotinamide mononucleotide (NMN), a NAD+ booster, increased the amount of NAD+ in both young and old mice. The level of NAD+ in aged mice treated with NMN more than doubled that of the untreated animals. Researchers also discovered that animals given NMN had greater ATP levels, indicating an increase in mitochondrial activity, in which the cells produce more energy.
“There’s clearly much more work to be done here, but if these results stand, then many aspects of aging may be reversible if caught early,” said Sinclair. According to the researchers, the development of tiny chemicals that block HIF-1's interference with cell communication or boost NAD+ levels may be a useful therapy for aging in the future.