NAMPT stands for nicotinamide phosphoribosyltransferase, a key enzyme involved in the production of NAD+ (nicotinamide adenine dinucleotide) through the salvage pathway. NAD+ is essential for energy metabolism, DNA repair, mitochondrial function and activating longevity associated proteins like sirtuins.
Because NAD+ levels naturally decline with age and this enzyme plays a central role in replenishing it, this enzyme is at the heart of longevity research and metabolic health strategies. Maintaining NAMPT activity is considered crucial for healthy aging, stress resistance and cellular vitality.
Biological function
NAMPT is the rate limiting enzyme in the NAD+ salvage pathway, which recycles nicotinamide (NAM), a form of vitamin B3, back into NAD+. This is the primary way our cells maintain NAD+ levels, especially in tissues with high energy demand like the brain, heart and muscles.
It supports:
- Mitochondrial energy production (through NAD+ in cellular respiration);
- Sirtuin activity, which regulates DNA repair, inflammation and metabolic health;
- Cellular stress resistance and survival under conditions like caloric restriction or oxidative stress.
Without adequate NAMPT activity, cells struggle to maintain their NAD+ pool, leading to dysfunction and faster aging at the molecular level.
NAMPT and aging
As we age, NAMPT expression declines, particularly in key metabolic and immune tissues. This contributes to a gradual reduction in NAD+ levels, which is a hallmark of aging. Low NAD+ is associated with:
- Mitochondrial dysfunction;
- Reduced DNA repair capacity;
- Chronic inflammation;
- Cognitive and metabolic decline.
Studies show that boosting NAMPT levels or supporting its activity can restore NAD+, improve energy metabolism and slow several aspects of biological aging. In animal models, enhanced NAMPT expression has been linked to improved tissue regeneration, better insulin sensitivity and extended lifespan.
Longevity research
NAMPT has attracted attention in aging science for its role in extending lifespan and healthspan in model organisms. Increased activity:
- Enhances sirtuin function, particularly SIRT1, which protects DNA and supports mitochondrial health;
- Improves resilience to metabolic stress;
- Mimics some effects of caloric restriction, which is known to extend lifespan in multiple species.
Interventions that raise NAD+ levels via the salvage pathway depend on this enzyme to be effective. For this reason, maintaining or boosting NAMPT is seen as a foundational strategy for cellular rejuvenation and longevity.
How to support NAMPT activity
Certain behaviors and compounds are known to support its function:
Lifestyle strategies
- Exercise, especially endurance and resistance training;
- Intermittent fasting and caloric restriction;
- Heat and cold exposure (sauna, cold plunges).
These stressors activate hormetic responses that increase its expression and enhance NAD+ recycling.
Nutritional support
- Foods rich in vitamin B3 (niacin, tryptophan);
- Polyphenols like quercetin, resveratrol and apigenin;
- Sulforaphane and other NRF2-activating compounds.
NAD+ precursors
- NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside) are converted into NAD+ via pathways involving NAMPT;
- Without sufficient NAMPT, the conversion of NMN and NR into usable NAD+ may be impaired.
These precursors are often used in supplement form in longevity protocols aimed at supporting mitochondrial health and energy metabolism.
NAMPT and chronic disease
NAMPT plays a dual role in health and disease. On one hand, its activity is protective against age related conditions such as:
- Type 2 diabetes and insulin resistance;
- Neurodegenerative diseases (Alzheimer’s, Parkinson’s);
- Cardiovascular dysfunction;
- Inflammatory conditions.
On the other hand, overexpression of NAMPT has been observed in some cancers, where elevated NAD+ supports uncontrolled cell growth. This makes it a complex and context dependent target, protective in healthy cells, but potentially harmful in malignant ones.
NAMPT is a critical enzyme that sustains cellular energy by supporting NAD+ biosynthesis through the salvage pathway. As NAD+ levels fall with age, preserving its activity becomes increasingly important for mitochondrial function, DNA repair, inflammation control and overall cellular resilience.
Supporting NAMPT through lifestyle, nutrition and targeted supplementation may offer one of the most promising strategies to promote healthy aging and extend healthspan.
