Why Longevity Experts Supplement with NMN and Resveratrol
Brilliant longevity researchers have significantly advanced our understanding of aging over the past two decades. With a prime focus on the role of a type of protein called sirtuins, one researcher now oversees two prominent labs that frequently release groundbreaking studies on aging.
Sirtuins are a class of enzyme proteins that are involved in DNA repair processes. If they were able to keep functioning optimally, sirtuins could protect us from the ravages of old age. The problem is that sirtuins need NAD+ and that declines dramatically as we age. That's why many longevity experts and thousands of other individuals across the world supplement with NAD+ activators (also called "precursors" or "boosters" like NMN and NR). All of this will be explained shortly, but first it's helpful to understand more about the aging process.
A really quick and insightful way to get an appreciation for this perspective on aging is to listen to a segment of a podcast with longevity expert Peter Attia, MD. I'll embed the short podcast below for your listening pleasure and then provide some details about some of the science that's mentioned in case it's unfamiliar to you.
The Nine Hallmarks of Aging
One of the first things that Dr. Attia and his guest explains is a widely accepted, pretty definitive, if not exhaustive, depiction of what constitutes aging.
2013, a group of Spanish scientists led by biochemist Dr. Carlos Lopez-Otin took a crack at identifying and explaining what they referred to as the "Hallmarks of Aging". Since then, their study has become one of the most referenced studies in the aging science literature.
These are the nine Hallmarks of Aging:
- Genomic instability (DNA damage)
- Telomere attrition (chromosome "caps" become less protective)
- Epigenetic alterations (gene expression becomes compromised)
- Loss of proteostasis (proteins are damaged)
- Deregulated nutrient sensing (imbalanced metabolism)
- Mitochondrial dysfunction (faltering energy)
- Cellular senescence (zombie cells)
- Stem cell exhaustion (tissues no longer get repaired)
- Altered cellular communication (cell "communication" is compromised)
These nine explain what goes awry as we age, but the pertinent question is, "what causes all of them?".
One Harvard researcher has developed a unifying theory of aging as the Information Theory of Aging, and it's largely based on that ninth Hallmark of Aging, "altered cellular communication."
"Information Theory" Of Aging
To describe the Information Theory of Aging, we use the analogy of digital and analog systems that store and transfer data (information) and declares that the fundamental cause of aging is a loss of cellular information that degrades over time.
Our genome (genetic code) is digital and thereby easy to preserve and replicate, as it's "written" in a linear sequence of four letters corresponding to two nitrogen-containing compounds: Purines (consisting of A and G, or adenine and guanine), and Pyrimidines (consisting of C and T, or cytosine and thymine). The genome stays very much intact as we age.
Our epigenome is analog. The other part of the "information" we inherit from our parents is epigenetic information. Epigenetics is the study of changes in organisms, like us, caused by modification of gene expression rather than alteration of the genetic code itself. This pattern of gene expression speaks to which genes are turned on, and when.
Each cell turns on only a fraction of its genes. The rest of the genes are repressed, or turned off. The process of turning genes on and off is known as gene regulation, which plays a critical part of normal development. Genes are turned on and off in different patterns during development to make brain cells look and act different from liver cells or a muscle cell, for example. Gene regulation also allows cells to react quickly to changes in their environments.
An excellent example of epigenetics at work is observable through the lens of identical twins whose genes are the same, but have very different lifestyles. Studies on identical twins hint on how environments and lifestyle change gene expression. Because they have the same immutable genes, researchers can determine how alterations in the twins' respective lifestyle choices and environments affect their epigenome differently. This addresses the age-old question of nature versus nurture - what aspects of a person originate from their DNA (from the above parlance, "digital information", and which come from their environment "analog information")?
The epigenetic/analog information acts in multiple dimensions: it adapts to what we eat and drink, if we exercise or surf the couch, and how much sleep we get - all of these are examples of what can influence how and when genes are being turned on or off, which is constantly happening.
This analog information operates in four dimensions, if you include time, but because it's analog, it doesn't last very long. Just as a vinyl record or cassette degrades over time, so does this epigenetic/analog information.
That's not the case with the digital information of the genome. Continuing with the analogy, genes might get scratched (say a break in the double helix strand) like a CD might, but because it's digital, the information is still there. The CD just needs to be polished to retrieve the information. Until that happens, however, the cells won't consistently read the "read" the right genes at the right time, and thus the cells lose their identity.
Yes, in effect, our cells have identity.
Cells know what they are - a heart cell versus a kidney cell, for example - but over time, various types of degradation to the genes can disrupt the clarity of the genetic information that tells the cells what they are. For instance, neuron cells may stop functioning as neurons and liver cells began to function more like neuron cells. This creates the various hallmarks of aging cited above.
How does the loss of gene regulation happen?
I'm now finally going to get back to sirtuins, which will lead us to why many researchers supplements with NMN and resveratrol.
Sirtuins, nicknamed “the longevity genes”, are a family of seven protein enzymes (in mammals) involved in regulating cellular processes, including the aging and death of cells and their resistance to stress. They remove acetyl tags from histones and other proteins and, by doing so, change the packaging of the DNA, turning genes off and on when needed. These critical epigenetic regulators sit at the very top of cellular control systems, controlling our reproduction and our DNA repair.
DNA breaks in chromosomes distract the sirtuin complex resulting in genes that inappropriately get turned on. If you forgot your high school biology, chromosomes are threadlike structure of nucleic acids and protein found in the nucleus of most living cells. They carry genetic information in the form of genes. Mammals like us have seven sirtuins.
Insults to the genome, such as a double strand break, distract sirtuins from their job of responding to various cellular stresses as they go into gene repair mode. Over the term of, say, an 80-year life, the cumulative damage caused by gene expression (getting turned on) when they should not is a good part of what makes us old.
Why Do Scientists Supplement With NMN and Resveratrol?
The most reliable research highlights the multi-faceted role of sirtuins. Sirtuins are enzymes that remove acetyl tags from histones and other proteins, and thereby change the packaging of the DNA, turning genes off and on when needed. These critical epigenetic regulators sit at the very top of cellular control systems, controlling our reproduction and our DNA repair.
Sirtuins require a molecule called NAD (nicotinamide adenine dinucleotide), which unfortunately declines substantially as we age. This loss of NAD - and resulting decline in sirtuin activity - is thought to be a primary reason our bodies develop diseases when we're old but not when we're young.
Moving from a reproduction function to a repair function, sirtuins order our bodies to "buckle down" in times of stress and protect us against the major diseases of aging. These remarkable sirtuins:
- Mute the chronic, overactive inflammation that drives diseases.
- Prevent cell death and boost mitochondria, the power packs of the cell.
- Go to battle with muscle wasting and bone loss.
- Improve DNA repair in mice, boost their memory, increase exercise endurance, and help them stay thin, regardless of what they eat.
This is not speculative; scientists have established all of this in peer-reviewed studies published in journals such as Nature, Cell, and Science, which are some of the most respected journals in academia.
So, the burning question is: "How do you keep your NAD levels from falling, thereby neutering the capacity of sirtuins to help us age better?".
To answer that you just have to look at why experts supplement with NMN and resveratrol.
They use NMN (Nicotinamide Mononucleotide) because it activates NAD+, the oxidized form of the coenzyme NAD (Nicotinamide Adenine Dinucleotide).
NMN and another NAD+ precursor/activator called NR (Nicotinamide riboside) have been widely studied. NR has been shown to increase levels of the NAD+ that sirtuins need to help us age better in both human and other animal models. Currently, there are human trials examining the effects of NMN on humans, which have yet to be published, but it's been extensively tested in other animal models by senior scientists, and has been shown to be both safe and effective.
Most of them take one gram of NNM powder (the same that ProHealth uses for our NMN Pro Powder), along with 500 mg of resveratrol (such as Natural Resveratrol), often mixed in yogurt every morning as yogurt contains some fat. Taking these supplements with fats improves their assimilation in the body.
Resveratrol has been studied in various animal models, from yeast to mice, and has been proven to improve their health, as well as lifespan. Researchers have demonstrated in hundreds of published studies that resveratrol supports mouse health in many ways.
Studies with humans aren't so clear. When resveratrol was given to human cells in culture dishes, they became resistant to DNA damage, but otherwise there's been no proof that it improves human healthspan or lifespan. These types of studies are challenging, given that humans have a long lifespan, and there are numerous ethical questions that must be resolved. In research conducted in one Harvard lab, it’s been found that treating mice with resveratrol makes them resistant to the negative side effects associated with eating a high-fat/Western diet, and their livers, arteries, and metabolic markers mimicked those of healthy, lean, and young mice when given the human equivalent of 250 mgs per day.