NMN can help reduce lung damage caused by cigarette smoke.

Cigarette smoking is widely recognized for its harmful health consequences, including its association with idiopathic pulmonary fibrosis (IPF), a lung disease often linked to aging and the accumulation of senescent cells. Recent research led by Dr. Zhang from the Southern Medical University in China delves into the potential of nicotinamide mononucleotide (NMN) to mitigate these effects.

Dr. Zhang and a team of researchers have conducted a study in the field of free radical biology and medicine, uncovering how NMN can aid in repairing damaged cells in mice exposed to cigarette smoke. Cigarette smoke leads to the accumulation of harmful molecules in the cell's mitochondria, promoting the development of aging cells. NMN activates autophagy, a process that helps remove these harmful molecules, potentially reducing cell aging and preventing IPF, particularly in adult smokers if this research extends to humans.

The Impact of Smoking on Cell Aging To examine the effect of smoking on cell aging, the researchers exposed indoor mice to cigarette smoke twice a day for 30 minutes over a span of four weeks. During this exposure, they observed that cigarette smoke accelerated the aging of lung cells. In laboratory experiments, they found that treating lung cells with a solution made from cigarette smoke also increased cell aging, indicating that cigarette smoke indeed hastens the aging of lung cells.

Impaired Autophagy and Cell Aging Previous research by Dr. Zhang and colleagues suggested that impaired autophagy plays a role in lung fibrosis caused by cigarette smoke. Autophagy acts as the cell's cleaning system. In this study, they sought to establish a connection between impaired autophagy and the accelerated aging of lung cells triggered by cigarette smoke since the precise role of autophagy in cell aging was not well-understood. They discovered that a protein called LC3-II, associated with autophagy, initially increased in lung cells exposed to the cigarette smoke extract (CSE) but then decreased. By using a drug called rapamycin to stimulate autophagy, they prevented the accelerated aging of lung cells caused by CSE. These findings suggest that although cigarette smoke initially enhances autophagy, it later diminishes the process that counteracts cell aging.

Harmful Molecules and Cell Aging Researchers have been interested in the build-up of reactive oxygen species (ROS) in the cell's mitochondria, as this has been linked to aging and cell aging. Dr. Zhang and colleagues aimed to determine if the accumulation of mitochondrial ROS was a result of impaired autophagy induced by cigarette smoke. They found 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 implies that impaired autophagy allows harmful mitochondrial ROS to accumulate, leading to cell aging.

NMN Enhances Autophagy and Reduces Cell Aging NMN is a crucial molecule serving as a precursor to another molecule called nicotinamide adenine dinucleotide (NAD+), which plays a significant role in cellular energy production. NMN also activates a protein called Sirtuin1 by increasing NAD+ levels. Sirtuin1 aids in removing acetyl groups from other proteins, activating them. In their study, researchers supplemented NAD+ levels with NMN to observe its impact on autophagy. They found that NMN promoted 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 uncovered by Dr. Zhang and colleagues, Sirtuin1 removes acetyl groups from the autophagy-regulating protein LC3-II, promoting autophagy, reducing mitochondrial ROS, and eliminating the build-up of aging cells. Using an inhibitor called Ex527 to block Sirtuin1 reversed the effects of NMN. This suggests that NMN therapy has the potential to restore autophagy and reduce the accelerated cell aging caused by cigarette smoke, which could help prevent diseases like IPF.

The researchers also found that smoking suppresses the activity of Sirtuin1, a protein that helps regulate cell functions. Additionally, they discovered 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.