This Journal contains some biochemical considerations about aging and will reference mitochondrial health, methylation biochemistry, and the chemistry of a class of compounds called sirtuins. A new anti-aging supplement from Designs for Health will be described which supports and enhances these life giving biochemical pathways.
A key molecule of healthy cellular function is known as nicotinamide adenine dinucleotide, which commonly goes by the abbreviated designation NAD+. This molecule is a coenzyme factor which is found in all living cells and is a key central molecule in mitochondrial metabolism. NAD+ is also the signaling molecule which activates sirtuin chemistry. I’ll offer information about the interconnection of NAD+ and sirtuin activation, as well as mitochondrial and methylation support for optimal longevity effects
This Journal considers NAD+’s role in the aging process and how to successfully supplement with NAD+ precursors like nicotinamide mononucleotide (NMN) to course-correct aspects of mitochondrial health, genome and immune integrity, brain function, and more. NMN is a direct precursor to the mitochondrial coenzyme NAD+ which is necessary for mitochondrial ATP production and a host of other life processes. NAD+ has never been stabilized to be taken as a stand alone supplement, but its levels in our biochemistry can be supported and elevated by taking its direct precursor NMN.
NAD+ plays a role in more than 500 reactions in the body, including energy production, metabolism, aging, gene expression, stress response, and DNA repair. Aging has been well linked to a deficiency of NAD+ and/or insufficient NAD+ for sirtuins which require it to properly perform necessary biochemical processes in the body.
Because NAD+ levels steadily drop with age, the repletion of NAD+ has become a dedicated focus in longevity research. Depletion of NAD+ in the aging process can negatively impact a multitude of core biochemical functions that influence healthspan and degenerative decline. A decline in NAD+ during aging is believed to be a major cause of disease and disability, such as hearing and vision loss, cognitive and motor dysfunction, immune deficiencies, auto-immunity, and the dysregulation of the inflammatory response chemistry which leads to arthritis, metabolic dysfunction and cardiovascular disease.
In mouse models NAD+ boosters have been found to prevent or treat a variety of different murine diseases. This research has prompted a search for NAD+ boosters that are safe and effective to use as supplements, as well as pharmaceutical versions, to mitigate diseases and the aging process.
Designs for Health’s new NAD+ boosting formulation
An important new addition in the Designs for Health nutritional product line is Liposomal NMN Synergy which can be purchased using this web store link. This formulation features nicotinamide mononucleotide in a pump bottle liposomal delivery system. The liposomal delivery ensures immediate and efficient absorption into the bloodstream and delivery to all cells.
Liposomal NMN Synergy is a potent formula containing nicotinamide mononucleotide (NMN) and trimethylglycine (TMG) to support healthy methylation chemistry and associated cellular pathways. The main ingredient, nicotinamide mononucleotide (NMN), is a direct and stable precursor to NAD+, critical for energy production, DNA repair, cell survival and the other benefits which are shown below. TMG is a methyl donor that supports the action of NMN. Liposomal NMN Synergy is the only NAD+ precursor using a liposome delivery for enhanced bioavailability.
Further biochemical considerations
This Journal considers the importance of mitochondrial health and maintenance as an important aspect of healthy aging, as well as the importance of balancing methylation support for optimal longevity effects.
Adenosine triphosphate (ATP) is the energy molecule of the cell, made in the mitochondria, that makes all of the biochemistry of life and health possible. Mitochondrial ATP production is dependent of a variety of nutritional substrates to help convert oxygen, proteins, fats, and carbohydrates into ATP. The end reason that we eat protein, carbohydrate, and fat and breathe oxygen is so that our cells can make ATP from these 4 substrates…one cell at a time.
Mitochondrial production of ATP from protein, carbohydrates, fats, and oxygen is dependent on critical cofactors: B vitamins, omega fats, carnitine, coenzyme Q10, lipoic acid, and magnesium. However, the most important and critical biochemical which participates in the production of ATP is NAD+.
NAD+ acts as a coenzyme in a number of the biochemical steps which convert food elements into ATP. Thus, ATP production is NAD+ dependent.
Cellular production of NAD+ drops off severely starting around age 50. All of our tissues age as a result of this decline, as well as a decline in a number of other biochemical processes. Our individual aging process follows a path which is dependent on our genetics, lifestyle decisions and activities (epigenetics), hormone levels and function, and the things we do to help mitochondrial health.
The health of mitochondrial chemistry is the most important aging/anti aging and disease prevention/recovery process that I know of. Accompanying this foundational cellular life chemistry is another ubiquitous umbrella chemistry known as methylation.
Two Journals written in 2014 cover mitochondrial and methylation biochemistry:
- Minding your Mitochondria…these important cellular organelles are foundational to life and deserve the foremost focus when considering anti-aging efforts. This is the cell site where the energy molecule of life, adenosine triphosphate, or, ATP, is made via the citric acid cycle (Kreb’s cycle) and the electron transport chain. NAD+ participates in key biochemical steps in these 2 pathways. The efficient and youthful production of ATP throughout our lives embues us with the energy currency for all cellular processes and biochemical reactions. Without healthy levels of ATP all cellular processes decline in efficiency…one cell at a time.
- Minding your Methylation…this broad class of our biochemistry involves the transfer of a methyl group which is made up of one carbon linked with 3 hydrogen atoms, or, CH3. In addition to assisting in the production of ATP, methylation chemistry plays a role in just about every biochemical process in our bodies.
Sirtuins
The much researched health benefits of NAD+ are achieved by signaling and activation of a class of protein molecules called sirtuins. This class of chemicals function as enzyme activators. Their activation and expression is dependent on NAD+ signaling.
Sirtuins are known as silent information regulators (SIR). Technically, these biochemicals are histone deacetylases requiring NAD+ as a signaling coenzyme for their enzymatic activity. Currently there are 7 classes of sirtuins which go by the labels of SIRT1 through SIRT7. These protein molecules play a variety of roles in cellular function, including energy homeostasis, cell cycle regulation, and apoptosis. Sirtuins (SIRT) are also known as NAD+consuming enzymes because NAD+ acts as a SIRT activator.
Here is a description of some things we know about the 7 sirtuins based on just some of the research:
SIRT1… This sirtuin has the most research. A 2017 study published in the International Journal of Molecular Medicine has found that SIRT1 is required for and supports mitochondrial biogenesis (1). According to a 2013 study published in PLoS One, it helps to regulate energy metabolism and supports the activation of thyroid T3 hormone (2).
According to a 2011 study published in Current Pharmaceutical Design, with the help of fasting, it may offer protection against neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease (3).
A 2007 study published in Nature has found that it may help the treatment of insulin resistance and diabetes (4). According to a 2017 study published in Frontiers in Endocrinology, SIRT1 may help to reduce the risk of age-associated weight-gain by supporting leptin sensitivity (5).
According to a 2011 study published in Hepatology, SIRT1 may help to support liver function and body homeostasis (6). Lastly, a 2010 study published in Biochemical and Biophysical Research Communications, SIRT1 may help human embryonic stem cell differentiation (7).
SIRT2…A 2012 study has found that SIRT2 may help to favorably modify mitochondrial activity and fatty acid metabolism (8). It may help to support metabolism and reduce the risk of obesity.
SIRT3…In a 2011 review published in Molecular Cell, SIRT3 may help to fight and reduce the risk of oxidative stress (9). According to a 2011 study published in Biochemical Journal, low levels of SIRT3 may be linked to insulin resistance and fatty liver disease (10).
SIRT4…A 2013 study published in Cancer Cell has found that SIRT4 may offer tumor-suppressive benefit (11). It may discourage mitochondrial glutamine metabolism and as a result, help to modulate metabolic response to DNA damage. According to a 2006 study published in Cell, SIRT4 may also help to reduce insulin secretion (12).
SIRT5…SIRT5 regulation has important effects on mitochondrial metabolism (13).
SIRT6…A 2010 review published in Trends in Biochemical Sciences has found that SIRT6 helps support genome stability and DNA repair. Low levels of SIRT6 may result in metabolic problems and age-related health issues (14). A 2010 review published in Trends in Biochemical Sciences has found that SIRT6 helps support genome stability and DNA repair. Low levels of SIRT6 may result in metabolic problems and age-related health issues (15).
SIRT7…This sirtuin is important for both DNA transcription and DNA repair mechanisms (16).
Here is a diagram to help you appreciate some of the effects of the sirtuin family of chemical signals.
The Importance of Sirtfoods
An important note about foods and sirtuins…Foods do not contain sirtuins, but certain foods are known to support and activate sirtuin pathways. These foods are known as sirtfoods.
Sirtfoods exert their positive influence on sirtuins by way of the polyphenol chemicals which are present in the food. Some polyphenol rich foods are: green tea, coffee, dark chocolate, berries, onions, asparagus, broccoli, grapes, red wine, kiwi, basil, rosemary, oregano, thyme, peppermint, cloves, pecans, cherries, and plums.
There are some references in the Associated Reading list at the end of the writing which cover the benefits of some of the common sirtfoods.
Summary and Conclusion
Seen below are diagrams which help summarize the important roles of NAD+ in the biochemistry of life.
The pie picture shown here displays a summary of the benefits of NAD+’s various roles in maintaining and enhancing our biochemical homeostasis, health, and aging.
NAD+ is a key signaling molecule that controls cell function and survival in response to environmental changes such as nutrient intake and cellular damage. Fluctuations in NAD+ impact mitochondrial function and metabolism, oxidation/reduction reactions, circadian rhythm, immune response and inflammation, DNA repair, cell division, protein-protein signaling, chromatin and epigenetics.
Since NAD+ levels steadily decline with age and lead to a decline in the function of cells and organs, NAD+ boosters can have positive physiologic effects on the health and survival of mammals by promoting cognitive and sensory function, gluconeogenesis in liver, lipogenesis in adipose tissue, insulin secretion in pancreas, and insulin sensitivity in muscle. NAD+ also promotes endothelial cell proliferation, protects against cardio- and cerebrovascular disease, regulates immune function and inflammation, and protects against acute injury in kidney. NAD+ promotes and extends fertility in both males and females.
NAD+ Boosting Supplement and Sirtuin Support Supplements
Containing 50 servings per bottle, Liposomal NMN Synergy has been formulated to contain 50 mg of nicotinamide mononucleotide (NMN) and 50 mg of trimethylglycine (TMG) per serving to support healthy aging and cellular function.
Recommended Use: Take 1 mL (approximately 2 pumps) and hold in mouth for 30 seconds before swallowing. Take on an empty stomach at least 10 minutes before meals. May be stirred into a small amount of water.
There are other supplements which have been researched and known to influence sirtuins in a beneficial way. The basic list includes:
- vitamin D
- melatonin
- omega 3 fatty acids
- zinc
- resveratrol
- quercetin
- EGCG
- magnesium
- vitamin B3 (niacin)
- amino acids
All of the supplements listed in this last paragraph are the same ones I have recommended for immune system support and boosting over the past year and a half.
Thank you for reading.
Signing off from Crestone and Beyond
Associated Readings
- NAD+: The Molecule of Youth? + Factors That Increase It…an extensive discussion on what NAD+ is, its benefits, the effects of low NAD+, and various ways to boost it.
- Lifespan: Why We Age–and Why We Don’t Have To…a book by geneticist David Sinclair, Ph.D., who researches in his lab at Harvard. This book goes into NAD+ and sirtuin pathways, as well as everything else which supports healthy aging.
- The Empowering Neurologist–David Perlmutter M.D., and Dr. David Sinclair…an informative one hour interview from 1-24-21 which covers many aspects of anti-aging wisdom.
- Therapeutic potential of NAD-boosting molecules: the in-vivo evidence…a technical writing from 3-6-19 authored by David Sinclair, Ph.D., and associates which appeared in Cell Metabolism. This article is dense, but informative. Some of the images in this Journal writing are from this article.
- Top Ten Sirtuin Foods for Good Health…there are various lists of sirtfoods which you can peruse and study and come up with your favorites. You can also explore some of the other sirtfoods which may not be common in your diet.
- Top 20 Sirtfoods/Sirtuin-Activating Foods And Benefits Of Consuming Them…”‘Sirtfoods’ is a term applied to foods that contain naturally occurring compounds known as polyphenols that have the potential to activate sirtuins.” This article covers some of the nutritional biochemistry of sirtfoods.
- The Ketogenic Diet…a writing on this website about the ketogenic diet. A benefit of keto dieting and intermittent fasting is sirtuin activation.
- Former Bear’s QB on Injury Recovery With NAD, Omega-3…Former professional quarterback Jay Cutler is using intravenous nicotinamide adenine dinucleotide (NAD) and high dose omega-3 fatty acids to help preserve his brain health; NAD is a vital signaling molecule and depletion is common in cases of neurodegeneration and concussions.