As we age, we experience a decline in our metabolism and metabolic function. This slow, steep decline increases our risk of age-related conditions, as our metabolism slows, our insulin sensitivity declines, our joints become less mobile, and our arteries less flexible, impeding healthy blood flow. We would all love a fountain of youth—an elixir to magically ward off the deterioration often associated with aging. The good news is there are novel therapeutics available right now that may have the ability to help preserve a more youthful metabolism and vitality.[1]
One key molecule at the front and center of healthy aging is NAD+ (nicotinamide adenine dinucleotide). It is found in all our cells and is often called our body’s own master “longevity” molecule. NAD+ is required for over 500 enzymatic reactions in our bodies and is fundamental to almost all biological processes. NAD+ was discovered early in the last century, in 1906. We produce lots of it when we’re young, but levels steadily decline with age.[2] [perfectpullquote align="full" bordertop="false" cite="" link="" color="" class="" size=""]By the time we are middle aged, levels of NAD+ have fallen to half of our youthful levels. [/perfectpullquote]
That’s a big problem, because the activity of critical signaling molecules in our body is utterly dependent on NAD+. Those molecules include ones with funny names, such as the sirtuins, often called protectors of the genome, and PARPs (Poly(ADP-ribose) polymerase) which are responsible for DNA repair.
To put it bluntly, according to Eduardo Chini, MD, PhD, of the Mayo Clinic's Robert and Arlene Kogod Center on Aging, “This decrease in NAD+ appears to be, at least in part, responsible for age-related metabolic decline."[3] And maintaining or restoring levels of NAD+ may have profound protective effects. Several studies on old mice have shown that giving the animals precursors to NAD+ can greatly improve their health.[4] Now human studies have begun.
Think of it this way: having lots of NAD+ is like having a checking account with ample funds. Everything you need to survive and thrive can be paid for. But as your NAD+ levels decline, you start bouncing checks, or utilizing your overdraft, for which you later have to pay extra in interest. What’s worse, your expenses have gone up as you age. You’ve accumulated more free radical damage, more wear and tear on your tissues, joints and organs, and more DNA errors and mutations. What do you really need? More NAD+!
You Don’t Have To Starve: How Studies on The Profound Benefits Of Calorie Restriction Shed Light On NAD+
A veritable goldmine of scientific research has shown that eating less—called calorie restriction—extends lifespan and delays illness and dysfunction in many creatures, from the smallest yeast organism to fish and mice. Similarly, extraordinary longevity in humans seems linked in part to calorie restriction. The longest-lived and healthiest people in the world live in what have been called “Blue Zones.” These are places on earth where it’s common to reach 90 or 100 while remaining active, vital and without succumbing to the typical diseases we associate with the elderly—and in every case the individuals share certain lifestyle factors. These include being physically active, being folded into community and family, eating a nutrient-dense, plant-based diet (not necessarily vegetarian, but rich in plant-based foods), and calorie restriction. The famously long-lived Okinawans follow a 2500-year old Confucian mantra before meals that reminds them to stop eating when their stomachs are 80% full. Other inhabitants of other Blue Zones eat their last meal of the day before sundown, and it’s the smallest meal.[5]
A reduction in calories of 30-40% triggers activity of the anti-aging sirtuins as well as a network of genes that have evolved to protect us during food scarcity.[6] In the words of geneticist David Sinclair, PhD, of Harvard Medical School, “Calorie restriction without malnutrition is considered the gold standard in biogerontology as the most robust way to delay ageing and age-related diseases.” In fact, Sinclair told Harvard Magazine that, “The interesting thing about calorie restriction is that we used to think the body was in some way slowing down, maybe in the number of heartbeats or production of free radicals. But it turns out that’s wrong….When we’re calorie restricting, what we’re really doing is telling the body that now is not the time to go forth and multiply. It’s time to conserve your resources, repair things better, fight free radicals, and repair broken DNA.”[7]
During calorie restriction, our cells engulf and clear out debris and damaged proteins and then recycle or dispose of them. Mitochondria also take the opportunity to repair themselves and divide, creating fresh, new mitochondria. Inside our cells, intracellular pathogens are dealt with, broken down and ferried away.[8],[9],[10] Remember that proverbial checking account? Calorie restriction is like wiping out all the overdrafts and extra charges and depositing new cash.
[perfectpullquote align="full" bordertop="false" cite="" link="" color="" class="" size=""]Nicotinamide adenine dinucleotide (NAD+) is thought to mimic the effects of calorie restriction, without the downsides (it can be hard to limit calories or fast for many people). Like calorie restriction, it activates sirtuins, which may be one of the main ways both methods work to slow aging.[/perfectpullquote]
And as NAD+ levels drop with age, the function of some sirtuins is also reduced.[11]
Sirtuins: The Secret Sauce in NAD+ Supplementation
Sirtuins are being studied as one of the most promising targets in healthy aging science.[12] Sirtuin expression is associated with increased longevity.[13],[14] Sirtuins are critical for cell metabolism and DNA repair, stress resistance, the formation of new mitochondria and regulation of inflammation. Sirtuins mobilize cells’ response to a wide range of stresses, including oxidative stress. Sirtuins play a central role in inflammation, cell growth, circadian rhythms, energy metabolism, neuronal function, and stress resistance.[15]
Scientists have been studying aging for a long time, and they’ve zoomed in on many possible triggers—from free radical damage[16] to shortening of little structures on our cells called telomeres, which protect our chromosomes and have been called cellular aging clocks.[17]
NMN: A Direct and Stable Precursor to NAD+, Helps Slow Aging and Restore Metabolism
The identification of molecules that safely maintain NAD+ levels in humans cannot come soon enough,” wrote David Sinclair and his colleague Michael Schultz in 2016. This is true, they wrote, “for patients who could benefit and those who hope to celebrate many more anniversaries.”[18]
[perfectpullquote align="full" bordertop="false" cite="" link="" color="" class="" size=""]NAD+ can be increased in several different ways, a primary one being supplementing with NMN[/perfectpullquote]
[19] Like NAD+, plasma NMN levels decrease with age.
In animal studies, supplemental NMN increases levels of NAD+ and leads to a wide array of remarkable effects.[20] NMN has been able to suppress age-associated weight gain, enhance energy metabolism and physical activity, improve insulin sensitivity, improve eye function, improve mitochondrial metabolism and prevent age-linked changes in gene expression.[21] Treatment of old mice with NAD+ precursors, such as NMN, markedly improves muscle function and reverses age-associated declines in muscle; NAD+ improves mitochondrial function and ATP production.[22]
Stem cells can be rejuvenated by raising NAD+ levels. Deterioration of adult stem cell function is correlated with aging.[23] Kidney function decreases with age, due largely to lower levels of NAD+ in aged kidneys and a decrease in sirtuin activity. Activation of sirtuins by raising NAD+ levels protects kidneys.[24]
Blood vessel flow is improved with NMN. Our organs and tissues rely on an abundant, rich microcapillary network to continually supply them with oxygen and nutrients as well as remove waste products. Treatment of old mice with NMN restored important aspects of blood vessel function, and increased the flexibility of arteries, enhancing blood flow.[25]
An interesting question is the delivery system for oral NMN: the body makes its own liposomal “vesicles” that transport NMN through plasma in the body. A liposomal version of NMN may well mimic the body’s own transport system, enhancing uptake and delivery, as science advances its understanding of the holy grail of reversing aging.
An ideal armamentarium for anti-aging might look like this, then:
- Maintain healthy levels of NAD+
- Maintain healthy levels of antioxidants like glutathione, Vitamin C, and lipoic acid
- Try to follow a “blue zone” lifestyle with a plant-based diet, exercise, connection to community, and sufficient ‘down time’ to relieve stress
- Include other important phytonutrients that are also associated with healthy aging, such as resveratrol, milk thistle, curcumin and quercetin
- Support methylation in a gentle way, with nutraceuticals like betaine (trimethylglycine) and active B vitamins.
- Do work that you love, and don’t forget to have fun!
References:
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[3]Specific enzyme linked to process of metabolic dysfunction in aging. Science Daily. Available at https://www.sciencedaily.com/releases/2016/06/160614155722.htm. Accessed January 1, 2020
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[19]Poljsak B. NAMPT-Mediated NAD biosynthesis as the internal timing mechanism: in NAD+ World, time Is running in its own way. Rejuvenation Res. 2018 Jun;21(3):210-224 View Abstract
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