Apigenin, Sleep, and Aging
For those following research into efforts to upregulate NAD+ levels to improve mitochondrial function, this paper is an interesting sidebar. Some degree of loss of NAD+ emerges from increased activity of CD38. Apigenin is a dietary supplement that can modestly influence both sleep and pace of aging, the latter in short-lived laboratory species at least. Apigenin can increase NAD+ levels by inhibiting CD38 activity. Like much of metabolism, this is all very interesting, but the effect sizes are nothing to write home about. If upregulating NAD+ levels is the goal, you'll do better by exercising. The fundamental flaw in so much of medical development, particularly in the supplement industry, is that few of the people involved seem to pay any attention to effect size. It is crazy! Effect size should be the first thing anyone looks for. Then side-effects. So much effort is, to my eyes, wasted on development programs for products with effects that are significantly worse than the results of exercise.
NAD+, a pivotal coenzyme central to metabolism, exhibits a characteristic decline with age. In mice, NAD+ levels can be elevated via treatment with apigenin, a natural flavonoid that inhibits the NAD+-consuming glycoprotein CD38. In animal models, apigenin positively impacts both sleep and longevity. For example, apigenin improves learning and memory in older mice, reduces tumor proliferation in a mouse xenograft model of triple-negative breast cancer, and induces sedative effects in mice and rats. Moreover, apigenin elongates survival in fly models of neurodegenerative disease and apigenin glycosides increase lifespan in worms.
Apigenin's therapeutic potential is underscored by human clinical studies using chamomile extract, which contains apigenin as an active ingredient. Collectively, chamomile extract has been reported to alleviate anxiety, improve mood, and relieve pain. Furthermore, dietary apigenin intake positively correlates with sleep quality in a large cohort of adults. Apigenin's electron-rich flavonoid structure gives it strong bonding capacity to diverse molecular structures across receptors and enzymes. The effects of apigenin extend beyond CD38 inhibition, encompassing agonistic and antagonistic modulation of various targets, including GABA and inflammatory pathways. Cumulatively, a large body of evidence positions apigenin as a unique molecule capable of influencing both aging and sleep. Further studies are warranted to better understand apigenin's nuanced mechanisms and clinical potential.