Key Pointers

  • NAD+ levels decline is a consequence of various environmental and lifestyle factors.
  • Aging is a natural phenomenon that impacts the progressive decline of NAD+ levels.
  • Age-related Macular degeneration is also associated with a decline in our NAD+ levels.

NAD+ is involved in the transportation of energy for various metabolic processes at the cellular level. However, it is equally affected by environmental factors such as food, population density, parasites, and pollutants. Furthermore, lifestyle factors such as alcohol use, smoking, lack of physical exercise, obesity, and unhealthy diet play a huge role in the further decline of our NAD+ levels.

Caloric imbalance and obesity are other factors believed to negatively impact NAD levels. The NAD levels change in response to the expressions received from NAMPT. Excessive intake of carbohydrates and a high-fat diet has been shown to decrease the NAMPT expression by 2-3-fold in the skeletal muscle and liver. Whereas, caloric restriction can have a significant positive impact on NAD levels.

Aging has an impact on the progressive reduction of NAD+ levels as the individuals age goes 40 and above. Improper function of mitochondria is considered a hallmark for possible metabolic impairments during the process of aging. Possibly, due to overexpression of CD38 gene consuming lesser oxygen with increased levels of lactate.

The most common mechanism involved in the aging process which impacts the NAD+ level decline is gene expression, decrease in mitochondria, DNA repair function, and inflammatory response, such a mechanism with growing age damages and disrupts the cellular function.

According to the research study, the scientist tried to understand why age-related NAD levels decline. There are two major pathways involved in the generation of NAD, the salvage pathway and the de novo pathway, de novo requires starch which can only be obtained from the diet. However, the salvage pathway can use the NR precursors from within the body for conversion into NAD.

The salvage pathway can also recycle molecules. The molecules like sirtuins use NAD and split up into different components to be used whenever needed. This pathway disrupts with age due to a decrease in enzymes NAMPT. The NAMPT decreases with age due to factors such as oxidative stress and healthy inflammatory markers leading to NAD levels decline with age.

Age-related macular degeneration is also associated with a further decline in levels of NAD. It is a multifactorial disease in which the retinal pigment epithelial photoreceptor cells decrease which are required for proper NAD+ metabolism. Similarly, the NAMPT levels are also associated with the decline of RPT levels. Thus, the reduced NAMPT directly affects the NAD metabolism leading to an altered de novo synthesis pathway.

Various animal model research studies have shown to improve retinal NAD+ metabolism with the use of supplementations; however, detailed studies are still required on the human model to confirm the role of age-related macular degeneration impact of NAD+ level decline.


To Conclude, the primary cause which impacts the decline of NAD levels within our body is age. It is believed that with age, cellular exhaustion leads to alteration in two major metabolic pathways, de novo and the salvage pathway. Diseases such as age-related macular degeneration and calorie imbalance are also associated factors equally involved in the negative impact of NAD level within our body.


  1. https://www.aboutnad.com/nad-levels-are-not-constant
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5088772/
  3. https://www.hindawi.com/journals/omcl/2020/2692794/