NAD+ is an essential molecule that plays a crucial role in various cellular processes, including gene expression, DNA repair, and metabolism. However, as we age, the levels of NAD+ in our bodies decline 1.
This decline in NAD+ levels is linked causally to numerous aging-associated diseases, including cognitive decline, cancer, metabolic disease, sarcopenia and frailty . 2
Several factors contribute to the drop in NAD+ that occurs with aging. These factors include a decrease in enzymes that help synthesize NAD+ and an increase in several proteins that degrade NAD+.
For example:
- Sirtuins: Sirtuins are a group of proteins that require NAD+ as a cofactor for their enzymatic activity. They play a role in regulating various cellular processes, including gene expression, DNA repair, and metabolism . 1
- Poly(ADP-ribose) polymerases (PARPs): PARPs are enzymes involved in DNA repair. They use NAD+ as a substrate to add poly(ADP-ribose) chains to target proteins, facilitating DNA repair processes . 1
- CD38: CD38 is a membrane-bound enzyme that catalyzes the conversion of NAD+ to cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP). These molecules are involved in calcium signaling and cellular communication . 1
- Alcohol dehydrogenase: Alcohol dehydrogenase is an enzyme that metabolizes alcohol in the liver. It uses NAD+ as a cofactor in the oxidation of alcohol to acetaldehyde . 1
In addition to these factors, other factors can also contribute to the decline of NAD+. For example:
- Oxidative stress: Oxidative stress is an imbalance between free radicals and antioxidants in the body. It can lead to damage to cells and tissues and contribute to aging. Studies have shown that oxidative stress can reduce NAD+ levels by inhibiting enzymes involved in its synthesis. 3
- Inflammation: Inflammation is a natural response of the immune system to injury or infection. However, chronic inflammation can contribute to aging and age-related diseases. Studies have shown that inflammation can increase the activity of CD38, leading to the degradation of NAD+ . 4
In conclusion, several factors contribute to the decline of NAD+ levels with aging.
While some of these factors are beyond our control, such as aging itself, others can be managed through lifestyle changes such as reducing alcohol consumption and managing inflammation through diet and exercise.
By understanding these factors and taking steps to mitigate their effects on our bodies, we can help maintain healthy levels of NAD+ and potentially reduce our risk of age-related diseases.
References:
- What Drives Aging? 1
- NAD+ metabolism and its roles in cellular processes during ageing. 2
- Age-related NAD+ decline - PMC - National Center for Biotechnology. 3
- NAD + biosynthesis, aging, and disease – PMC. 4