Aged Lung Cells Protected from Functional Decline with NMN
The decline of functioning in the aged, non-proliferating lungs (senescence) can induce disease, which researchers may prevent with nicotinamide mononucleotide (NMN) in mice.
Highlights
- NMN protected aged mice's lungs from entering stress and an age-induced state called senescence, which might help lung disease.
- NMN treatment inhibits lung scarring-induced lung structural damage.
- This is the first study to show that NMN might prevent and protect against lung cell aging, which can lead to disease.
When our lungs grow old, the alveolar epithelial cells that facilitate oxygen exchange to the blood fall out of function and diminish in number. The activity and number of these cells drop with age, but scientists believe it has something to do with their entering a non-proliferating state known as senescence.
The molecule NMN has been shown for the first time to decrease cell senescence and promote lung health in old mice, according to a study published in MedComm by Wei et al from China's National Clinical Research Center for Geriatrics. They determined that NMN lowers levels of age-related proteins in mouse lungs and alleviates chemically-induced and senescence-associated lung damage by giving mice 500 mg/kg/day of NMN through drinking water.
“Dietary supplementation of NMN might be a new and effective way to prevent and reduce aging-related lung diseases and stress-induced lung injury in the future,” proposed Wei and colleagues.
Falling Lung NAD+ Levels During Aging
NMN is a precursor to nicotinamide adenine dinucleotide (NAD), which is a critical molecule for metabolism and DNA health that declines with age in several cell types and organs, including the lungs. Cardiovascular diseases, neurodegenerative conditions, and metabolic problems have all been linked to NAD+ level reductions in older people, and research has shown that NMN improves various age-related illnesses in mice. But whether it aids in lung aging and senescence had not previously been investigated until now.
NMN Reduces the Buildup of Age-Associated Proteins
Wei and colleagues tested NMN's effects on the two proteins p16 and p21 that are implicated in aging in mice to see if it prevents lung tissue degeneration and AEC senescence. During the course of AEC senescence, the p16 protein inhibits cell division and proliferation, according to research. The team discovered that NMN reduced levels of this protein in mouse lungs.
The researchers found that NMN altered levels of p21, a protein that links DNA damage accumulation to cell proliferation cessation during aging in mice. In the lungs, the decrease in p16 and p21 suggests that NMN prevents lung tissue from becoming senescent and protects it throughout aging.
NMN Prevents Lung Cells From Entering Senescence
To see whether NMN protects against AEC aging via a separate mechanism, Wei and colleagues investigated the effect of the NAD+ precursor on cells that had been induced to undergo senescence in two distinct ways. When grown in laboratory dishes, NMN administration reduced the number of lung cells that entered replicative senescence — a condition in which cells can no longer proliferate after undergoing too many divisions — by up to 90%.
Wei and colleagues also treated the cells with a toxic antibiotic called bleomycin, which has been shown to induce lung cell aging. Following treatment with bleomycin, they discovered that NMN reduced the number of senescent cells significantly. These findings suggest that NMN protects against both excessive growth and stress-induced senescence.
NMN Protects Lung Structure and Function Under Stress
Wei and coworkers treated mice with bleomycin to induce lung tissue damage, then inhaled the drug to destroy their lungs. When these mice were given NMN, however, their lungs showed less destruction.
Mice that were treated with NMN had less inflammatory cells in their lungs and had smaller lung weights, than did mice that received bleomycin. These findings imply that NMN therapy helps prevent senescence-associated lung scarring by reducing the number of inflammatory cells in the lungs and lowering overall lung weight. These findings provide strong proof that NMN improves AEC age-related senescence.
NMN May Provide Protection Against Age-Related Lung Disease
“Our data suggested that NMN could effectively alleviate the replicative and stress-induced senescence of [alveolar epithelial cells],” said Wei and colleagues. The researchers found that NMN increased NAD+ levels, preventing age-associated lung cell senescence. The results imply that low NAD+ levels may contribute to aging.
Furthermore, NMN has the potential to treat and prevent cell senescence linked to low NAD levels. “It provides a preventive and therapeutic approach for aging-related chronic lung diseases and lung injury caused by external stimuli.” In the future, however, Wei and coauthors predict that NMN's dietary supplementation might be a novel, successful approach to prevent and treat age-related lung diseases and stress-induced respiratory trauma.
