National Institute on Aging Scientists Restore Age-Related Smell Loss with NAD⁺ Booster

Scientists discover that NAD+ declines with age in the olfactory bulb — the brain region involved in sense of smell — and restore smell loss with NAD+ booster nicotinamide riboside in old mice.

Key Points:

NAD+ declines with age in the olfactory bulb of mice.
NAD+ precursor, nicotinamide riboside (NR), increases the remaining lifespan of aged mice.
NR improves odor detection in aged mice.

A little-known side effect of aging is loss of smell. Increasing evidence even points to the loss of smell as an early indicator of Alzheimer’s and Parkinson’s disease. Now, scientists from the National Institute of Aging have found that NR may mitigate age-related smell loss.

Dan and colleagues report in Aging Cell that loss of smell is an early marker of aging and is associated with DNA damage, inflammation, and NAD+ decline. The NAD+ precursor, NR, mitigates this loss of smelling capacity while also increasing lifespan.

“Our findings indicate that both DNA damage repair and inflammation contribute to olfaction decline, which is partially preserved by NAD+ supplementation,” say the authors.

Nicotinamide Riboside Protects Against Olfactory Decline

By evaluating olfaction — sense of smell — in mice of increasing age, Dan and colleagues demonstrated that olfaction, including odor detection and sensitivity to odors declines with age. The NIH researchers also found that inflammation and DNA damage markers increase with age, and NAD+ levels fall with age in the olfactory bulb. These findings suggest that these cellular defects in the smell center of the brain contribute to age-related olfaction loss.

(Dan et al., 2023 | *Aging Cell*) **NAD+ Declines with Age in the Olfactory Brain Region.** Compared to young 3-month-(M)-old mice, NAD+ progressively declines in the olfactory bulb with increasing age.

NR boosts NAD+ levels and has previously been shown to alleviate DNA damage and inflammation. By placing NR in the drinking water of aged (24-month-old) mice for eight months, Dan and colleagues showed that DNA damage and inflammatory markers in the olfactory bulb tended to be reduced. Furthermore, NR treatment increased the lifespan of the mice, which was likely due to boosting NAD+ in other tissues.

(Dan et al., 2023 | *Aging Cell*) **Nicotinamide Riboside Increases Remaining Lifespan.** Compared to aged mice not treated with NR (green), NR-treated aged mice (blue) live longer.

For the odor detection test, Dan colleagues buried food then recorded how long it took for food-deprived mice to smell the location of the food. The amount of time it took to unbury and retrieve the food was also measured. It was found that NR-treated aged mice were faster than untreated aged mice at finding and retrieving the buried food, suggesting that NR mitigates odor detection loss. However, NR did not help the mice improve on other olfaction tests, such as the odor sensitivity test, indicating that NMN partially improves olfactory function.

(Dan et al., 2023 | *Aging Cell*) **Nicotinamide Riboside Restores Odor Detection.** Compared to aged mice not treated with NR (green), NR-treated aged mice (blue) find (left) and retrieve (right) buried food faster, indicating improved odor detection.

NAD+ Declines in Multiple Brain Regions

The findings of Dan and colleagues suggest that NR could help treat age-related smell loss. However, this is the first study to explore how boosting NAD+ can affect our sense of smell as we age. Still, this study reveals yet another brain region where NAD+ declines with age in mice. Other brain regions include the hypothalamus, important for regulating body-wide homeostasis, and the hippocampus, vital for memory consolidation. This implies that boosting NAD+ could help with multiple brain-related aging defects, including olfaction loss, memory loss, and dysregulated homeostasis, which has implications for many behaviors, including sleep and eating habits.