Key Points:
- After taking two grams of NR daily, aged COPD patients saw drastically lowered sputum levels of a protein associated with airway inflammation and cellular senescence—a dysfunctional cellular state linked to aging.
- As a precursor to nicotinamide adenine dinucleotide (NAD+), NR treatment more than doubled blood NAD+ levels, confirming the precursor’s NAD+-boosting capabilities.
- NR treatment was also associated with a trend toward reduced pace of epigenetic aging—an estimate of age based on the analysis of DNA chemical modifications (known as methylation patterns).
COPD, an incurable disease associated with smoking and aging, accounts for approximately 5% of deaths globally, making it the fourth-leading cause of mortality worldwide. Moreover, declining levels of NAD+—an essential molecule regulating metabolism, DNA repair, and immunity—have been proposed to contribute to COPD and aging more generally. Along those lines, the effect of restoring cellular NAD+ with precursors like NR in patients with COPD had not been examined.
Now, published in Nature Aging, Scheibye-Knudsen and colleagues from the University of Copenhagen in Denmark report that replenishing NAD+ with NR drastically lowers the inflammatory and senescence-promoting protein IL-8 in the sputum of aged patients with COPD. In further exploratory analyses, the Denmark-based researchers found that NR treatment more than doubled blood NAD+. Additionally, NR treatment was found to trend toward slowing the pace of epigenetic aging. The findings suggest that NR could serve as a viable treatment option for patients with COPD.
“Our study demonstrates that supplementation with NR reduced airway inflammation and increased NAD+ levels in whole blood,” say Scheibye-Knudsen and colleagues.
NR Treatment Was Associated with Lowering Airway Inflammation, More than Doubling NAD+, and Slowing Aging
IL-8 has been tied to an inflammatory response in COPD patients and serves as an aggravator of cellular senescence—a cellular state associated with tissue dysfunction and aging. For these reasons, Scheibye-Knudsen and colleagues examined whether NR treatment could lower IL-8 levels in the sputum of aged COPD patients. Intriguingly, they found that treatment with NR for six weeks was associated with a 52.6% reduction in sputum IL-8. This finding supports the possibility that NR lowers airway inflammation and reduces the occurrence of cellular senescence.
Since supplementing with NR has been linked to higher blood NAD+, the Denmark-based research team sought to confirm that six weeks of NR treatment boosts whole blood NAD+. Indeed, they found that NR more than doubled blood NAD+, confirming results from previous studies.
Because the study’s data suggests NR lowers sputum IL-8 and possibly impedes the occurrence of cellular senescence, the researchers analyzed whether NR has a broad effect on epigenetic age—an age estimate based on DNA methylation patterns. Their results suggest that NR supplementation trends toward slowing the rate of aging. Thus, these data support the notion that NR works to lower inflammation and hinder the accumulation of senescent cells to possibly slow the pace of aging.
Longer Human Studies Needed to Find Whether NR Improves Lung Function in Patients with COPD
As for limitations associated with the study, Scheibye-Knudsen and colleagues did not find that NR treatment improved lung function. This, according to the research team, was expected, though, since the treatment period of 6 weeks was too short to predict lung function improvements. Accordingly, follow-up studies on the order of six months to a few years may associate longer-term NR treatment with enhanced lung function in COPD patients. Only studies providing NR treatment for longer durations can give a better idea of whether long-term NR supplementation improves lung function in patients with COPD.
Along those lines, daily treatment with NR for longer periods may confer other effects, such as slowing the rate of biological aging even more than what Scheibye-Knudsen and colleagues observed in patients with COPD. In the current study, the research team found that NR treatment conferred a general trend toward reducing the pace of biological aging. Still, the possibility looms that longer-term NR treatment would make these results more robust so that the pace of aging is lowered significantly.
Moreover, the researchers found that NR had no clear effect on the pace of biological aging for study participants with healthy lungs. For this reason, more human studies are necessary to discern whether NR only lowers biological age in patients with organ dysfunction, such as reduced lung function. Longer study durations could also help parse out whether NR given over durations longer than six weeks may slow the pace of biological aging in healthy, aged individuals.
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