If you’ve started researching longevity supplements, you’ve probably run into a wall of confusing terminology fast. NAD+, NMN, NR, sirtuins, mitochondria, biological age. These terms matter, because understanding what they mean is the difference between building a supplement routine that actually makes sense and just buying whatever sounds impressive on a label.
This glossary defines the core concepts in plain language, grounded in the published science.
The Terms
Biological Age
A measure of how old your cells and tissues function relative to your chronological age. Two people who are both 55 years old may have very different biological ages depending on their genetics, lifestyle, nutrition, and cellular health. Biological age is assessed through biomarkers such as DNA methylation patterns and metabolic markers. Unlike chronological age, biological age is considered modifiable through lifestyle and targeted supplementation.
Biosynthesis Pathway
The sequence of biochemical steps the body uses to produce a molecule. In the context of NAD+ supplementation, the biosynthesis pathway refers to the series of conversions that turn precursor molecules like NMN or NR into NAD+. NR is converted to NMN, which is then converted to NAD+. NMN skips the first conversion step, entering the pathway one step closer to the final molecule. The efficiency of this pathway influences how well a given precursor raises NAD+ levels in tissue.
Cellular Energy (ATP)
ATP (adenosine triphosphate) is the primary energy currency of a cell. It is produced inside the mitochondria through a process that requires NAD+ as a key cofactor. When NAD+ levels decline with age, mitochondrial energy production becomes less efficient, which is associated with reduced stamina, slower recovery, and broader metabolic changes. Supporting NAD+ levels through precursors like NMN is one strategy used to support healthy ATP production as part of a longevity protocol.
Chronological Age
The number of years a person has been alive. Chronological age is fixed and cannot be changed. It is distinguished from biological age, which reflects the functional state of cells and tissues and is considered more relevant to longevity research. Most modern longevity science focuses on biological age rather than chronological age as the more meaningful measure of health trajectory.
Coenzyme
A small, non-protein molecule that binds to an enzyme and is required for that enzyme to carry out its function. NAD+ is one of the most important coenzymes in human biology, participating in hundreds of metabolic reactions. Unlike vitamins, which are required in small amounts primarily as structural cofactors, NAD+ is actively consumed during cellular processes like DNA repair, which is why its levels can decline meaningfully with age and metabolic stress.
DNA Repair
The cellular process of identifying and correcting damage to the DNA sequence. DNA is damaged constantly by oxidative stress, UV radiation, and normal metabolic activity. Efficient DNA repair is essential for genomic stability and is one of the hallmarks of healthy aging. NAD+ is a required substrate for PARP enzymes, which are among the primary DNA repair mechanisms in human cells. Declining NAD+ with age is associated with reduced DNA repair capacity, which has implications for cellular aging and long-term health.
Epigenetic Clock
A biological tool used to estimate biological age based on patterns of DNA methylation, chemical modifications to DNA that change predictably with age. The Horvath clock, developed by UCLA researcher Steve Horvath, is one of the most widely cited epigenetic aging clocks. Epigenetic clocks are used in longevity research to assess whether interventions, including diet, exercise, and supplementation, influence the rate of biological aging at a cellular level.
Hallmarks of Aging
A framework published in the journal Cell in 2013 (and updated in 2023) describing the core biological processes that drive aging. The original framework identified nine hallmarks including genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. NAD+ decline intersects with several of these hallmarks, particularly mitochondrial dysfunction, genomic instability, and deregulated nutrient sensing.
Liposomal Delivery
A formulation technology that encases an active ingredient inside a lipid (fat) bilayer called a liposome, which mimics the structure of a cell membrane. Because cell membranes are also lipid-based, liposomal delivery is thought to support absorption by allowing the liposome to fuse with or be taken up by cells more efficiently than standard oral delivery. Several NAD+ precursor and antioxidant supplements, including NMN and glutathione, are sometimes available in liposomal formulations. Bioavailability benefits vary by compound and individual physiology.
Mitochondria
Organelles found in nearly every cell in the body, often described as the cell’s powerhouses. Mitochondria are responsible for producing the majority of the cell’s ATP through a process called oxidative phosphorylation, which requires NAD+ as a key input. Mitochondrial function declines with age, and mitochondrial dysfunction is considered one of the primary hallmarks of aging. Supporting mitochondrial health through NAD+ precursors, CoQ10, and antioxidants is a central strategy in most longevity supplement protocols.
NAD+ (Nicotinamide Adenine Dinucleotide)
A coenzyme found in every living cell, involved in hundreds of metabolic reactions. NAD+ plays a central role in converting nutrients into cellular energy (ATP), activating sirtuins and PARP enzymes involved in DNA repair, and regulating circadian rhythms and cellular stress responses. NAD+ levels decline significantly with age, with research suggesting a drop of roughly 50% between the ages of 40 and 60. Because NAD+ cannot be efficiently absorbed as a supplement in its intact form, supplementation strategies focus on precursor molecules like NMN and NR that the body converts into NAD+.
NAD+ Precursor
A molecule the body uses as a building block to synthesize NAD+. Because orally supplemented NAD+ has poor bioavailability, precursors are the primary strategy for raising NAD+ levels through supplementation. The most clinically studied NAD+ precursors are NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside). Both enter the NAD+ biosynthesis pathway at different points and have been shown to raise blood NAD+ levels in human clinical trials. Niacin (vitamin B3) is also a NAD+ precursor but is associated with flushing side effects at higher doses.
Nicotinamide Mononucleotide (NMN)
A naturally occurring molecule and NAD+ precursor found in small amounts in foods such as edamame, broccoli, and avocado. As a supplement, NMN enters the NAD+ biosynthesis pathway one step before NAD+ itself, making it a more direct precursor than NR. Research published since 2020 has demonstrated that oral NMN supplementation raises blood NAD+ levels in humans and has shown associations with improved metabolic markers in clinical trials. A dedicated transporter protein (Slc12a8) identified in intestinal cells supports direct cellular uptake of NMN. NMN is available in capsule, powder, and liposomal forms.
Nicotinamide Riboside (NR)
A form of vitamin B3 and NAD+ precursor that is converted by the body into NMN before becoming NAD+. NR has a longer track record of published human clinical research than NMN, with trials beginning around 2016. Multiple randomized controlled trials have confirmed that oral NR supplementation safely raises NAD+ levels in healthy adults. NR is widely available as a supplement and has an established safety record across numerous studies.
Oxidative Stress
An imbalance between free radicals (reactive oxygen species) and the body’s antioxidant defenses. Free radicals are produced naturally during cellular metabolism but can damage DNA, proteins, and cell membranes when they accumulate faster than the body can neutralize them. Oxidative stress increases with age and is linked to accelerated cellular aging, inflammation, and chronic disease risk. Antioxidant supplements including glutathione, resveratrol, and CoQ10 are commonly used to support the body’s oxidative stress defense systems.
PARP Enzymes (Poly ADP-Ribose Polymerases)
A family of enzymes that use NAD+ to detect and repair DNA damage. When DNA is damaged, PARP enzymes are activated and consume NAD+ as part of the repair process. Because PARP activity is NAD+-dependent, declining NAD+ levels with age can reduce the efficiency of this DNA repair mechanism. This relationship is one of the primary reasons NAD+ is of significant interest in longevity research: maintaining NAD+ availability supports the cellular infrastructure that protects genomic integrity over time.
Sirtuins
A family of seven proteins (SIRT1 through SIRT7) that regulate a wide range of cellular processes including DNA repair, inflammation, metabolism, and stress response. Sirtuins are sometimes called longevity proteins because of their association with extended lifespan in animal models and their role in pathways activated by caloric restriction and exercise. Sirtuins require NAD+ to function, which is a key reason that maintaining NAD+ levels is considered important for longevity biology. Resveratrol is among the compounds studied for its potential to support sirtuin activation.
Slc12a8 (NMN Transporter)
A protein identified in intestinal cells that facilitates the direct transport of NMN into cells. The discovery of Slc12a8 as a specific NMN transporter, described by researchers at Washington University School of Medicine, helped clarify how NMN is absorbed and moved into tissues without first needing to be broken down. This finding supported the rationale for NMN supplementation as a direct NAD+ precursor strategy. The transporter’s activity has been shown to increase with age in some tissues, which researchers have interpreted as a compensatory response to declining NAD+ levels.
Telomeres
Protective caps at the ends of chromosomes, similar in function to the plastic tips on shoelaces. Telomeres naturally shorten each time a cell divides, and telomere length is considered a marker of cellular aging. When telomeres become critically short, cells stop dividing and may enter a state called senescence. Telomere length is one of several biological age markers used in longevity research. Lifestyle factors including chronic stress, poor diet, and smoking are associated with accelerated telomere shortening, while consistent exercise and certain nutritional strategies have been associated with preserving telomere length.
Senescence (Cellular)
A state in which a cell permanently stops dividing but does not die. Senescent cells, sometimes called zombie cells, accumulate with age and secrete inflammatory signaling molecules that can impair the function of surrounding healthy tissue. The accumulation of senescent cells is considered one of the hallmarks of aging and has been linked to age-related conditions including chronic inflammation, tissue dysfunction, and metabolic changes. Research into senolytics, compounds that selectively clear senescent cells, is an active area of longevity science.
Medical Disclaimer: This content is for informational and educational purposes only and is not intended as medical advice. Supplements are not intended to diagnose, treat, cure, or prevent any disease. Always consult a qualified healthcare provider before starting any new supplement regimen.