Cigarette smoking is widely acknowledged for its detrimental health effects, one of which is the development of idiopathic pulmonary fibrosis (IPF), a lung disease often tied to aging and the accumulation of senescent cells. Recent research suggests that nicotinamide mononucleotide (NMN) holds the promise of countering these effects.
Led by Dr. Zhang from the Southern Medical University in China, a team of researchers has explored the NMN benefits for lung health, particularly in individuals exposed to cigarette smoke. This article delves into NMN's potential to rejuvenate damaged cells, addressing the accelerated cell aging caused by cigarette smoke and offering hope for those at risk of IPF. Explore the connection between cigarette smoke, senescent cells, and NMN's potential to mitigate lung disease.
A group of researchers led by Dr. Zhang from the Southern Medical University in China has conducted a study in the field of free radical biology and medicine. They found that a substance called nicotinamide mononucleotide (NMN) can help repair damaged cells in mice exposed to cigarette smoke. They discovered that cigarette smoke causes harmful molecules to accumulate in the cell's powerhouses called mitochondria, which promotes the creation of aging cells. When NMN encourages a process called autophagy, it helps remove these harmful molecules, reducing cell aging and potentially preventing IPF, especially in adult smokers, if this research applies to humans.
Smoking Causes Lung Cells to Age
To test the impact of smoking on cell aging, the researchers exposed indoor mice to cigarette smoke twice a day for 30 minutes, over four weeks. During this exposure, they found that cigarette smoke made lung cells age faster. In laboratory experiments, they observed that treating lung cells with a solution made from cigarette smoke also increased cell aging. This strongly suggests that cigarette smoke speeds up the aging of lung cells.
Impaired Autophagy and Cell Aging
Previous research by Dr. Zhang and colleagues suggested that impaired autophagy played a role in lung fibrosis caused by cigarette smoke. Autophagy is like the cell's cleaning system. So, in this study, they aimed to link impaired autophagy to the accelerated aging of lung cells triggered by cigarette smoke because the exact role of autophagy in cell aging was not clear. They found that a protein called LC3-II, which is related to autophagy, initially increased in lung cells exposed to the cigarette smoke extract (CSE) but then decreased. When they used a drug called rapamycin to stimulate autophagy, it prevented the accelerated aging of lung cells caused by CSE. These findings suggest that although cigarette smoke initially boosts autophagy, it later reduces the process that counteracts cell aging.
Harmful Molecules Contribute to Cell Aging
Researchers have been interested in reactive oxygen species (ROS) building up in the cell's energy-producing structures, called mitochondria, because this has been linked to aging and cell aging. Dr. Zhang and colleagues wanted to know if the accumulation of mitochondrial ROS was caused by impaired autophagy induced by cigarette smoke. They discovered that treating lung cells with CSE increased mitochondrial ROS levels, but using a compound called mitoquinone that clears ROS protected the cells from aging. This means that impaired autophagy allows harmful mitochondrial ROS to accumulate, leading to cell aging.
NMN Boosts Autophagy and Reduces Cell Aging
NMN is an important molecule, a precursor to another molecule called nicotinamide adenine dinucleotide (NAD+), which plays a crucial role in cellular energy production. NMN also activates a protein called Sirtuin1 by increasing NAD+ levels. This protein helps remove molecular tags called acetyl groups from other proteins, activating them. In their study, the researchers supplemented NAD+ levels with NMN to see how it affected autophagy. They found that NMN encouraged autophagy in lung cells and reduced cell aging. Autophagy-related LC3-II levels increased after exposure to CSE when NMN was added, and NMN lowered markers of cell aging.
In the pathway for lung fibrosis that Dr. Zhang and colleagues discovered, Sirtuin1 removes acetyl groups from autophagy-regulating protein LC3-II, promoting autophagy, reducing mitochondrial ROS, and removing the buildup of aging cells. When they used an inhibitor called Ex527 to block Sirtuin1, it reversed the effects of NMN. This suggests that NMN therapy could potentially restore autophagy and reduce the accelerated cell aging caused by cigarette smoke, which could help prevent diseases like IPF.
The researchers also discovered that smoking suppresses the activity of Sirtuin1, a protein that helps regulate cell functions. Additionally, they found that activating Sirtuin1 and boosting NAD+ levels can restore its activity and prevent cell aging.
This study sheds light on how smoking contributes to lung diseases like IPF. However, more research is needed, particularly clinical trials involving humans, to determine if the benefits of NMN in reducing aging cell buildup and IPF could apply to people who smoke.
