Article Review: Nrf2, Guardian of Healthspan and Gatekeeper of Species Longevity?

Sanjay Gupta in his book “Chasing life, a quest for immortality” discusses the lengths and costs many people take to stay young and healthy. The anti-aging industry is such a huge multi billion dollar industry. Could it be possible that a discovery could have been made that could be the guardian of health span or even a gatekeeper of longevity?

There are so many interesting articles on Pubmed regarding Nrf2, but this one gives an excellent summary of what NRF2 activation can do for the body. Entitled: “Nrf2, a Guardian of Healthspan and Gatekeeper of Species Longevity.”Sanjay Gupta in his book “Chasing life, a quest for immortality” discusses the lengths and costs many people take to stay young and healthy. The anti-aging industry is such a huge multi billion dollar industry. Could it be possible that a discovery could have been made that could be the guardian of healthspan or even a gatekeeper of longevity?

This article was the result of a study completed and published in 2010, and presented at the symposium “Metabolism, Life History and Aging” in Seattle, Washington Jan 3-7, 2010. Credit goes to Kaitlyn N. Lewis,James Mele, John D. Hayes, and Rochelle Buffenstein for the research and discoveries. More about them can be obtained by reading the full study.

Aging impacts everyone! Anti aging remains a huge market, especially as the baby boomers have started reaching retirement age and are looking to slow down their aging.

The article introduces readers to NRF2, as follow. “The transcription factor Nrf2 is constitutively expressed in all tissues, although levels may vary among organs, with the key detoxification organs (kidney and liver) exhibiting highest levels.” The authors continue, “The Nrf2-signaling pathway mediates multiple avenues of cytoprotection by activating the transcription of more than 200 genes that are crucial in the metabolism of drugs and toxins, protection against oxidative stress and inflammation, as well as playing an integral role in stability of proteins and in the removal of damaged proteins via proteasomal degradation or autophagy.”

This information is HUGE. Nrf2 has the ability to turn on the body’s own survival genes (over 200 of them) to start producing survival enzymes the same way as it did when the body was young. The big marketing buzzword over the past few decades has been “antioxidants”. It is now marketed on cereals, supplements, chocolates, fruits and berries, juices and even sodas. We predict that as word gets out about Nrf2, the “master regulator” of aging, it will become one of the the next “buzzwords” just like the term antioxidant has become.

“Through their combined interactions is the guardian of healthspan, protecting against many age-related diseases including cancer and neurodegeneration. We hypothesize that this signaling pathway plays a critical role in the determination of species longevity and that this pathway may indeed be the master regulator of the aging process.”

We will not cover all of the history to the discovery of Nrf2 and its anti-aging properties. The link above takes the reader to a full discussion of the history.

Nrf2 – A Protector

“Nrf2 plays a central role in cytoprotection, by detoxifying and eliminating ROS, xenobiotics and electrophilic carcinogens, as well as removing damaged proteins and organelles”. The authors discuss how Nrf2 activation inhibits the formation of free radicals (known to be the cause of over 200 diseases). There are studies and reports that show NRF2 products having on average a 40% reduction in oxidative stress in as little as 14 days.

Roles of Nrf2

There are many documented roles for Nrf2. This article discusses a few.

1) Detoxification

The body produces harmful byproducts of stress known as toxins. Toxins from food, pollutants, or even infections. The impact of these toxins result in disease, aging and even death. Quoting from the article “Nrf2 is the primary responder to such toxins and upregulates expression of several compounds and enzymes (NQO1, GSH, GST) that promote the efficient neutralization, conjugation and concomitant elimination of the toxins.”

2) Stability and turnover of proteins

When proteins become destabilized in the body the correlation to neurological diseases becomes quite high. This correlation has been observed in diseases such as Alzheimer’s and Parkinson’s disease. Activation of Nrf2 once again has remarkable benefits. The article explains, “Induction of Nrf2 preserves proteasome function in human fibroblasts and extends replicative lifespan up to 65% by reducing the levels of ROS and oxidized proteins.”

3) Cellular integrity

When DNA gets damaged in can replicate through all the cells of the body. The article describes how Nrf2 can actually repair DNA and cell damage. “Nrf2 also interacts with p53, the tumor suppressor transcription factor widely regarded as the guardian of the genome. p53 regulates cellular pathways of response to stress that may lead to cell-cycle arrest, repair of DNA, cellular senescence and apoptosis.”

4) Inflammation reduction

“Recent data also reveal that Nrf2 signaling plays an important role in reducing the inflammatory response.” We won’t go into all the scientific explanation here. You are welcome to read the full article for that. It explains how wounds can heal quicker. Beyond just healing quicker, inflammation reduction is critical in the treatment and prevention of many disease states. Quoting further, “Nrf2-induced repression of the inflammatory system has widespread implications for many diseased states. Chronic inflammation is implicated in the etiology of several degenerative human diseases and promotes the pathogenesis and progression of autoimmune disease, asthma, neurodegeneration (e.g., Parkinson’s and Alzheimer’s disease), pulmonary fibrosis, osteoarthritis, colitis, renal failure, cardiovascular disease, atherosclerosis, and cancer”.

Nrf2 studies show that ” For example, the down-regulation of pro-inflammatory factors appears to have a profound beneficial effect on cardiovascular function and has made Nrf2 a novel target in the maintenance of cardiac health.”

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