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 .
However, in healthy cells, it appears that β-Lapachone may be beneficial, as the results of this new study suggest . 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.
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.
 Shi, F. D., & Ransohoff, R. M. (2010). Nature killer cells in the central nervous system. In Natural Killer Cells (pp. 373-383). Academic Press.
 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.