Breathing Easy: Raising NAD+ With NMN Combats Aging of Lung Cells

Respiratory and lung health have been at the top of many people’s minds over the last year and a half, with lots of attention understandably focused on viruses and pathogens that affect our airways and breathing abilities. After about age 35, the function of our lungs gradually declines with each passing year, leading to increased susceptibility to respiratory-related illness in older age. So, researchers have been looking at ways to fight back on this declining respiratory function in order to better support the lung health of older adults or those with lung injuries.

One such approach comes from Fang and colleagues based out of the West China Hospital in Chengdu, China. Their research involves the compound nicotinamide mononucleotide (NMN), a precursor to the vital molecule NAD+ (nicotinamide adenine dinucleotide.) In this study published in the journal MedComm, supplemental NMN is revealed for the first time as a promising candidate for fending off respiratory aging on a cellular level.

The ABCs of AECs

Aging lungs show progressive reductions in both the quantity and quality of cells known as alveolar epithelial cells (AECs). These cells make up the respiratory epithelium — cells that line the inside of the respiratory tract and actively prevent inhaled and infectious particles from entering the lungs. In addition to maintaining a protective physical barrier, AECs are highly involved in facilitating the body’s vital oxygen-carbon dioxide gas exchange, regulating inflammatory and immune responses, and repairing lung tissue after injury or damage.

Much of the underlying mechanisms behind respiratory aging involve increased rates of AEC senescence — the accumulation of dysfunctional, zombie-like cells that undergo irreversible growth arrest but remain in the body. Senescent cells leave a trail of inflammatory secretions and cellular debris behind and can alter gene activity, contributing significantly to the progression of aging and disease. Therefore, many researchers look to compounds that may help the body naturally clear out or reduce these zombie cells — like NMN.

Why We Need NAD+

NMN supplies the body with the tools it needs to produce NAD+, a coenzyme needed by every cell in the body, helping other enzymes and proteins to function properly. However, despite its essentiality, NAD+ levels are known to decline with age. Keeping NAD+ levels elevated is thought to slow down the aging process and support the health of our cells and organs with each passing year — including the AECs of the lungs and respiratory system.

In another recent study, researchers found that injecting NAD+ into the lungs of rats significantly increased lung function, blood flow, and oxygenation capacity. NAD+ also diminished the inflammatory response, supporting the theory that declining NAD+ levels play a role in respiratory aging. However, the effects of supplemental NMM in live animals had not yet been reported — until now, with the work by Fang and colleagues.  

Reducing Respiratory Cell Senescence With NMN

The China-based research team underwent two experiments, looking at rates of cellular senescence in both middle-aged mice and AEC cell cultures. In mice which were the equivalent of about 50 in human years, Fang and colleagues found high levels of alveolar cell senescence and proteins that inhibit cell growth. After supplementing the mice with NMN at a dose of 500 mg/kg/day for two months — equivalent to about 3 grams of NMN in humans — the numbers of both senescent cells and inhibitory proteins were reduced.

They also assessed how young mice with senescence that was induced by a specific medication were affected by supplemental NMN. While the medication markedly increased senescent cell rates and apoptosis — programmed cell death — of AECs, adding NMN effectively reversed it. Plus, NMN improved lung appearance and reduced lung weight (indicating less scarring or fluids in the lungs) and promoted a healthier inflammatory response. Lastly, Fang and colleagues found that adding NMN to a culture of lung epithelial cells also inhibited the age-related increase in senescence that contributes to respiratory aging.

Breathing Easy

For the first time, this novel research shows how boosting NAD+ levels through supplemental NMN supports healthier lungs and may slow down the process of lung aging by reducing senescent cell load. As poor respiratory health is a leading concern of older adults — especially in the climate of 2020 and 2021 — NMN could prove a preventive or therapeutic option for supporting the respiratory system. 

While we don’t have available research on how NMN affects lung health or senescence of alveolar epithelial cells in humans, this study provides a valuable jumping-off point. As Fang and colleagues conclude, “Dietary supplementation of NMN might be a new and effective way to prevent and reduce aging‐related lung [conditions] and stress‐induced lung injury in the future.”

References: 

Chuquimia OD, Petursdottir DH, Periolo N, Fernández C. Alveolar epithelial cells are critical in protection of the respiratory tract by secretion of factors able to modulate the activity of pulmonary macrophages and directly control bacterial growth. Infect Immun. 2013;81(1):381-389. doi:10.1128/IAI.00950-12

Fang T, Yang J, Liu L, Xiao H, Wei X. Nicotinamide mononucleotide ameliorates senescence in alveolar epithelial cells. MedComm (Beijing). 2021;2(2):279-287. Published 2021 May 27. doi:10.1002/mco2.6