Anti-aging and the science of nicotinamide riboside

B vitamins are a group of water-soluble vitamins that each play a unique role in different cellular processes. These vitamins are crucial for various metabolic reactions in the human body and include B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B7 (biotin), B9 (folic acid), and B12 (cobalamin).

In this category, NR is classified under the B3 category and functions as the precursor of nicotinamide adenine dinucleotide (NAD+), which is an important coenzyme present in all living cells. NAD+ plays a significant role in numerous cellular processes, including energy production, cell repair, and gene regulation. Emerging research indicates that the lack of NAD+ can lead to impaired cellular function, a phenomenon that is closely related to aging and age-related diseases.

The journey of NR from obscurity to scientific recognition reflects human curiosity and the creativity of science. This compound was first discovered in the early 20th century, around 1944, as a growth factor for the bacterium "Haemophilus influenzae". The early discovery of this substance led to it not receiving sufficient attention for a long time until the mid-21st century, when a research team led by Dr. Charles Brenner began to reveal its potential untapped value and discovered the pathway for converting NR to NAD+. More specifically, they discovered the enzymes used by eukaryotic cells (cells with a nucleus, present in all animals, plants, fungi, and single-celled organisms) to convert NR to NAD+, thereby revealing a two-step conversion pathway known as the "NRK pathway".

Role of NAD+ in healthy aging

With the increasing scientific prominence of NR, there has been a larger, concurrent surge in the understanding of its close partner, NAD+. This uptick in the importance of NAD+ has unfolded at a pace that highlights its growing association with aging and age-related diseases. Its emergence as a potential central player in aging is due to its two primary functions, cellular energy production and repair.

During cellular respiration, NAD+ and its reduced form NADH participate in redox reactions, which help generate adenosine triphosphate (ATP), the main energy currency of the human body. If NAD+ is insufficient, this cycle will be affected, leading to reduced energy production and decreased cellular function.

NAD+ also plays a crucial role in the cell repair mechanism. It serves as a substrate for different types of repair enzymes (known as poly(ADP-ribose) polymerases (PARPs) and Sirtuins), which use NAD+ to perform their repair functions. The activity of these repair enzymes has been shown to increase with age and exposure to metabolic stress factors, resulting in a corresponding decrease in NAD+.

Previously, it was believed that NAD+ was a conserved cellular resource, but now it is increasingly associated with age, metabolic stress factors, and diseases. Excessive alcohol consumption, long-term exposure to ultraviolet radiation, immune stress, and a sedentary lifestyle are all metabolic stress factors associated with a decrease in NAD+. In clinical and experimental studies, repeated exposure to these metabolic stress factors has been proven to reduce NAD+ levels in cells and tissues, leading to dysfunction and the occurrence of diseases.

Scientists have observed that in numerous organisms ranging from single-cell yeast to mice and humans, the NAD+ level decreases as these organisms age. Although the debate over the fundamental cause of this decline (whether it is due to aging over time or the gradual accumulation of stress factors) continues, it is becoming increasingly clear that NAD+ is not a constant resource.

Furthermore, its consumption can lead to a series of age-related functional disorders, including mitochondrial dysfunction, increased inflammation, decreased cell recovery ability, and impaired cell repair ability. These changes are associated with the development of various age-related diseases, such as neurodegenerative diseases like Parkinson's disease, and cardiovascular diseases like heart failure.

Understanding the impact of these metabolic stressors and diseases on NAD+ levels is crucial for developing strategies to mitigate their effects and potentially restore NAD+ homeostasis.