NRF1 and NRF2: What Should You Know

Mitochondria are the energy-producing organelles in the cells. Having healthy mitochondria is crucial to keep our cellular functions and overall health at peak. Mitochondrial function has been noted as a determinant of life span. However, as we age, mitochondrial health and function decline, leading to problems in cells, tissues, organs, and the body.

Key takeaways:
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    NRF1 and NRF2 turn on genes that are important in mitochondrial function.
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    NRF1 and NRF2 supplements include resveratrol, quercetin, sulforaphane, curcumin, naringenin, and agmatine. The recommended intake is two capsules after breakfast.
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    NRF1 and NRF2 exert pro-longevity effects by preserving mitochondrial functions and combating oxidative stress.
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    There is still insufficient clinical evidence as to how much of each NRF activator supplements we should take every day to have significant results.

According to the mitochondrial theory of aging, age-associated mitochondrial dysfunction is due to the accumulated damage induced by ROS (Reactive oxygen species). As a result, aging-related disorders that are stemming from mitochondrial dysfunction arise. Scientists have found that NRF1 and NRF2 genes are important in combating mitochondrial dysfunction and cellular aging.

What are NRF1 and NRF2?

NRF1 and NRF2 are transcription factors, proteins, that activate genes related to specific pathways or molecular processes. Specifically, they turn on important genes that are involved in making new mitochondria and the induction of oxidative phosphorylation, a major metabolic pathway in the energy-generation process. As we age, virtually every aspect of our mitochondrial health deteriorates. NRF1 and NRF2 target mitochondrial health. They are in charge of mitochondrial turnover, which means that as the mitochondria begin to degrade, they take out the damaged ones and replace them with healthy ones.

How are they different?

NRF1 and NRF2 work best together to promote mitochondrial function. However, the NRF1 pathway works better when there is NRF2 signaling, which helps and works with NRF1. They have overlapping targets, but also have are more exclusive targets, which may indicate that they also play distinct roles individually.

The main difference between NRF1 and NRF2 is that NRF1 turns on critical genes involved in metabolism, cellular development, energy production, and mitochondrial DNA transcription and replication, while NRF2 activates the expression of antioxidant genes to attenuate the oxidative damages during inflammation, injury, or disease.

NRF1 and NRF2 supplements

Currently, the only NRF supplements available on the market are NRF activators. NRF1 supplements turn on the NRF1 pathway, which oversees most of the health of your mitochondria. NRF2 activator supplements activate pathways to support the natural production of antioxidants, reduce cellular stress, and repair cells, specifically the mitochondria. NRF2 activators are thought to have a wide range of extraordinary health effects, including the reduction of inflammation and pain, protection against diabetes (by lowering insulin resistance), and defense against several immune and degenerative disorders.

Supplements that activate the NRF pathway:

  • Resveratrol;
  • Quercetin;
  • Sulforaphane.
  • Curcumin;
  • Naringenin;
  • Agmatine.

How do they work?

NRF1 and NRF2 affect mitochondrial function at multiple levels. They assist the mitochondria's critical energy-formation processes. So that the cell can keep doing its important jobs, it must make sure that enough mitochondria are made, copied, repaired, and regenerated, and those unhealthy mitochondria are thrown away.

Mitochondrial ATP is needed for the breakdown and removal of unhealthy mitochondria, the production of new mitochondria, and the improvement of the cell's antioxidant and detoxification systems. The NRF2 signaling pathway is an important master regulator of cell survival, defense, and aging healthily. It is like the head of our internal defense system; it protects us as we age. Primarily, the NRF2 pathway protects our body from oxidative stress and the damage it causes.

How to take NRF1 and NRF2 supplements

The best way to use NRF supplements is to take two capsules after breakfast in the morning. NRF1 and NRF2 supplements are not recommended for underage or pregnant individuals. Some supplements need to be discussed with a doctor first, and some are not good for people with weak immune systems. However, there is still insufficient clinical evidence as to how much of each NRF activator we should take every day to have significant results.

Can I take these at the same time?

NRF1 and NRF2 activators can be taken at the same time primarily due to their separate, but complementary signaling pathways. NRF1 is responsible for the reproduction, rejuvenation, and repair of mitochondria, whereas NRF2 is the regulator of defense against oxidative stress and the damage it causes to our body.

NRF1 and NRF2 for longevity

The natural imbalance between free radicals and antioxidants in our bodies is called "oxidative stress”. Oxidative stress happens when insufficient antioxidant molecules are available to keep the number of free radicals created in balance. This leads to "oxidation," a gradual and accumulative effect on the cell that makes the cell "rust" and speeds up the natural aging process. Even more free radicals are produced with increased energy use and expenditure. Mitochondria are constantly being replaced as part of a cell's normal function. This natural turnover of mitochondria is necessary for cells to stay alive. Also, mitochondrial biogenesis is necessary to keep a cell alive since it is the production of new mitochondria.

NRF1 and NRF2 are very important to make new mitochondria and the development of the cell's antioxidant and detoxification systems to slow aging and promote healthy aging.

Side effects of NRF supplements

It is important to note that excessive NRF supplementation may trigger unfavorable effects. These include the following:

  • headache;
  • stomach pain;
  • rash;
  • vomiting.
  • diarrhea;
  • fever;
  • wheezing;
  • swelling.

While NRF activation is beneficial in many situations, having the pathways always activated can be damaging to the body. In addition, in pre-cancerous and malignant cells, NRF1 and NRF2 may confer therapeutic resistance due to their antioxidant effects and could protect cancer cells against chemotherapeutic drugs.

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