Human Plasma NAD+ Metabolome Dysregulation with Age

This article here talks about age related circadian rhythm dysregulation. I tend to take 500mcg of melatonin at the same time every night before bed (I don't take it if I'm past that time).  It may help maintain that rhythm if dosage is increased with age, maybe an extra 500mcg each decade past 40. Just a hypothesis based on this idea of sleep, circadian rhythm, and the brain cleaning that goes on with cerebral spinal fluid during sleep, (especially side sleeping position) and aging.  I'm sure this is all connected somehow but for the past several years now I've mastered the rhythm I think. I even wrote a guide on optimizing sleep.

 

Furthermore, in the context of the self-hacked article you linked, in light of this thread and the original post information, he's wrong that precursors like NR don't require NAMPT, because of the excess of NAM from NAD+ use that could result.

I recently came across this: 

https://www.wired.co...ves/?verso=true 
 

 

Take a chemical called nobiletin, which is found in the oily peel of some orange and kumquat species and has proven itself one of Chen’s most promising candidates. The small molecule binds to one of the core clock proteins responsible for stabilizing the 24-hour cycle. When his team administered nobiletin to mice that were fed a high-calorie diet (Chen describes it as an “all-McDonald’s every day” diet), they stayed slim, even as control mice packed on nearly twice their body weight in just 10 weeks. Nobiletin also improved other markers of healthy metabolism, like fasting glucose and cholesterol levels.

Chen’s team published those results in 2016, and more recently, they’ve tested nobiletin’s potential to reverse some of the common ailments associated with aging. As we get older our metabolism slows down, which impacts everything from exercise endurance and heat production to the ability to sleep for long stretches of time. Evidence suggests this metabolic tail-off is tied to mitochondrial burnout. Our cells’ energy factories just aren’t outputting as much as they used to. And why is that? Because mitochondrial function is closely regulated by our circadian clocks, which also get weaker as we age—they tick more quietly. In work that is currently under review, Chen’s group used nobiletin to restore the circadian clocks in muscle cells of aged mice. As a result, the mice were stronger, slept better, and lived longer than their untreated counterparts. “Chronologically they were 28 months, but they behaved much younger,” Chen says.

Encouraged by these results, he is now expanding into an even more ambitious project—testing whether or not circadian-enhancing drugs could be used to treat Alzheimer’s disease, the debilitating neurodegenerative condition that will affect about 10 percent of the US population before the middle of the century. 

Life Extension seems to agree with their ingredients for "Circadian Sleep" that has 50 mgs nobiletin per capsule. Only one I could find that had any nobiletin unless normal orange peel capsules have some, but it is not called out.