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Today, we want to spotlight a recent study showing that boosting nicotinamide adenine dinucleotide (NAD+) levels in mice prevents age-related hearing loss.

What is β-Lapachone?

β-Lapachone is a quinone-containing compound that was originally isolated from the lapacho tree in South America. It is worth noting that this tree has been used as a herbal medicine for a number of South and Central American indigenous peoples and that the bark of the tree is sometimes used for making a herbal tea called taheebo.

The compound has been shown in previous studies to have potential as an anti-cancer agent, and, in one study, it appeared to induce reactive oxygen species-mediated (ROS) autophagic cell death in U87MG malignant glioma cells [1].

However, in healthy cells, it appears that β-Lapachone may be beneficial, as the results of this new study suggest [2]. The compound was used to boost levels of NAD+ in the mice and appears to improve mitochondrial function, reduce inflammation, reduce ROS and oxidative stress levels, and encourages biogenesis.

Standard C57BL/6 mice were used for this study; these mice are not a model of any disease and are not engineered to experience accelerated aging, as progeric mice that are commonly used in aging research are, so these results are relevant to normal aging, not an artificial emulation of it. Using these normal mice instead of progeric mice makes it more difficult to dismiss results of potential interventions against aging.

Age‐related hearing loss (ARHL) is a major neurodegenerative disorder and the leading cause of communication deficit in the elderly population, which remains largely untreated. The development of ARHL is a multifactorial event that includes both intrinsic and extrinsic factors. Recent studies suggest that NAD+/NADH ratio may play a critical role in cellular senescence by regulating sirtuins, PARP‐1, and PGC‐1α. Nonetheless, the beneficial effect of direct modulation of cellular NAD+ levels on aging and age‐related diseases has not been studied, and the underlying mechanisms remain obscure. Herein, we investigated the effect of β‐lapachone (β‐lap), a known plant‐derived metabolite that modulates cellular NAD+ by conversion of NADH to NAD+ via the enzymatic action of NADH: quinone oxidoreductase 1 (NQO1) on ARHL in C57BL/6 mice. We elucidated that the reduction of cellular NAD+ during the aging process was an important contributor for ARHL; it facilitated oxidative stress and pro‐inflammatory responses in the cochlear tissue through regulating sirtuins that alter various signaling pathways, such as NF‐κB, p53, and IDH2. However, augmentation of NAD+ by β‐lap effectively prevented ARHL and accompanying deleterious effects through reducing inflammation and oxidative stress, sustaining mitochondrial function, and promoting mitochondrial biogenesis in rodents. These results suggest that direct regulation of cellular NAD+ levels by pharmacological agents may be a tangible therapeutic option for treating various age‐related diseases, including ARHL.

Conclusion

This is yet another study involving the restoration of NAD+ levels, which fall during aging and are part of deregulated nutrient sensing, which is a secondary hallmark of aging. NAD+ also contributes to the effective repair of our DNA, and genomic instability is a primary hallmark of aging. Therefore, there is no doubt that NAD+ is an important player in aging as a whole.

While boosting NAD+ levels with compounds such as β-Lapachone does not address the underlying damage that leads to the decline of NAD+ in the first place, such studies hint at what we might expect to happen should those underlying causes be targeted directly.

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Literature

[1] Shi, F. D., & Ransohoff, R. M. (2010). Nature killer cells in the central nervous system. In Natural Killer Cells (pp. 373-383). Academic Press.

[2] Kim, H. J., Cao, W., Oh, G. S., Lee, S., Shen, A., Khadka, D., … & Kwak, T. H. (2019). Augmentation of cellular NAD+ by NQO1 enzymatic action improves age‐related hearing impairment. Aging cell, e13016.

About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, and, Keep me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.
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