This month's favorite book excerpt is from "NutriSearch Comparative Guide to Nutritional Supplements for the Americas", 6th Edition, by Lyle MacWilliam, BSc, MSc, FP. You'd think a comparative guide may just have charts, but this one also does a good job of explaining some of the science behind the nutrition. As many of my favorite books, this one is great from beginning to end, I'm just gonna drop a few pages about Nrf2 and Redox Balance, for tasters. Hope you're science top heavy, because this excerpt is like reading a biochemistry text book. But it's about what may well be the mechanics of aging (and possibly, anti-aging).
p. 47 - Nrf2 and Redox Balance
Nrf2 is a nuclear transcription factor that is the master regulator controlling redox balance in the cell. Nrf2 is responsible for the transcription of over 500 genes in the human genome, most of which have protective functions. The protein is expressed in all cells of the body at low levels, with the highest concentrations found in the kidney, muscle, lung, heart, liver, and brain. Best known for its ability to choreograph redox balance through the stimulation of highly coordinated endogenous antioxidant activities, Nrf2 does much more than that: it activates detoxification mechanisms to disarm and remove harmful xenobiotics and heavy metals; it produces major anti-inflammatory changes; it stimulates mitochondrial biogenesis and improves mitochondrial function. There is also strong evidence that the Nrf2 signalling pathway plays a key role in the determination of species longevity and may, indeed, be the master regulator of both healthspan and lifespan.
In a good example of what we said earlier about nature being decidedly conservative, Nrf2 -- despite having a half-life (the time required for one-half the quantity of any biomolecule in a living organism to be metabolized or eliminated through normal biological processes) of only 20 minutes -- is kept under tight control in the cytoplasm, bound to a protein called KEAP1 (Kelch-like ECH-associated protein-1). When things are quiet, KEAP1 maintains an awareness of toxic influences, such as environmental poisons, and electrophilic and reactive oxygen species (ROS). KEAP1 anchors Nrf2 to scaffolding proteins in the cytoplasm, eventually attaching it to a molecule of ubiquitin (known as the "kiss of death" for proteins). This action initiates a journey that carries the Nrf2 molecule to a proteasome (a protein complex in the cytoplasm that is responsible for degrading wastes such as damaged proteins by cleavage of the peptide bonds between the constituent amino acids), an organelle (small organ within the cell) where proteins are constantly being degraded and recycled for further use by the cell.
However, when the Nrf2/KEAP1 complex detects any of a wide range of signals, including the presence of reactive species (ROS, RNS), inflammation, injury, UV light, cigarette smoke, and other environmental toxins, a reduction in available energy supply, or the presence of electrophiles (chemicals attracted to electrons), its physical shape changes. This loosens KEAP1's grasp on Nrf2, allowing it to escape and cross the nuclear membrance.
Once inside the nucleus, Nrf2 binds to the promoter sequence of a protein of DNA near the Electrophile Response Element (EpRE) region, (formerly -- and incorrectly -- known as the Antioxidant Response Element or ARE). This region is a collection of hundreds of genes involved in many aspects of cellular protection. These include: the production of antioxidant molecules and enzymes to maintain redox balance; the suppression of inflammation; the activation of key longevity genes; and the stimulation of mitochondrial biogenesis and autophagy, the house-keeping activities that all cells need to stay healthy (we'll discuss these processes in the next chapter).
The spectrum of diseases positively affected by Nrf2 is wide. Cardiovascular diseases; neurodegenerative diseases, such as Alzheimer's, Parkinson's and Lou Gehrig's disease; metabolic diseases, including type 2 diabetes; autoimmune diseases; chronic kidney diseases; and several cancers all respond to Nrf2 signalling. Reviews describe the Nrf2 pathway as a "master regulator of the aging process," and one that "plays a critical role in the determination of species longevity." One review submits that the "finding that raising Nrf2 (in the body) may be useful in prevention and/or treatment of this list of diseases seems almost too good to be true," adding, "Nrf2 is likely to be the most important health promoting approach into the foreseeable future."
...."What must be done to activate the available Nrf2 in a way that will promote health and longevity?"
The next section of the chapter is about how Nrf2 is activated. It's all very interesting, but that gives you an idea.