Science of
Redox Signaling Molecules
The science of redox signaling molecules is based on their roles as cellular activators and cellular messengers. In order to carry out daily functions and adapt to sudden changes, our cells are constantly communicating, releasing signals to each other. These signals are redox signaling molecules! They go on to activate biological pathways, or convey messages between cells.
Known as a subset of reactive oxygen species (ROS), redox signaling molecules are tiny molecules like H2O2. Because cells need to communicate quickly, every cell produces ROS as natural products of metabolism. Efficiently, each signal triggers the next in a cascade effect.
Simply put, “redox” is a scientific term for “reduction-oxidation reaction,” which enables electron transfers important to many biological processes. Redox signaling molecules are therefore critical for life-sustaining cellular repairs, and for supporting metabolic functions that provide you energy. [3]
Cellular Activators — When redox signaling molecules operate as cellular activators, they act like on/off switches for various pathways. This includes those responsible for tissue regeneration, cell differentiation, immunity, and gene expression. [8] Biological pathways control the body’s production of necessary molecules. So by activating (and deactivating) pathways, redox signaling molecules allow us to physically adapt to altering conditions, both internal and external. [12]
Cellular Messengers — When your cells detect harmful viruses and bacteria, or cell damage from stressors and aging, redox signaling molecules are sent as cellular messengers, informing your body to respond to threats and make repairs. [7] Because redox signaling molecules are so small, they are quickly released and absorbed. Once a cell receives a signal, it’s able to relay its own redox signaling molecules, and pass the message to other cells in a cascade effect. [6] This makes them ideal messengers for fast cellular communication, and ensures a responsive immune system.
FAQ Redox Signaling
About Redox Signaling:
Redox signaling is important because many biological pathways depend on it! From immune support, to blood vessel formation, to cell proliferation and development, natural aging, hormone production, cognition, and heat generation— all these processes work because redox signaling molecules activate them. Redox signaling molecules are also used to convey information between cells, as part of cellular communication!
Source: Sies, H., Belousov, V.V., Chandel, N.S. et al. Defining roles of specific reactive oxygen species (ROS) in cell biology and physiology. Nat Rev Mol Cell Biol 23, 499–515 (2022). https://doi.org/10.1038/s41580-022-00456-z
Most ROS (and subsequently redox signaling molecules) are naturally produced in the body from 2 sources:
1. the Mitochondria, as a product of a type of metabolism known as mitochondrial respiration. Mitochondria are found in every human cell, with the only exception being red blood cells!
2. NADPH Oxidase, an enzyme found in white blood cells, that helps notify immune cells of harmful pathogens and eliminating them.
The reactions that create ROS are known as redox reactions!
Source: Sies, H., Belousov, V.V., Chandel, N.S. et al. Defining roles of specific reactive oxygen species (ROS) in cell biology and physiology. Nat Rev Mol Cell Biol 23, 499–515 (2022). https://doi.org/10.1038/s41580-022-00456-z
Redox signaling molecules work as chemical signals! When cells need to communicate, they release redox signaling molecules. They diffuse in the space between cells, until they latch onto receptors on other cells. Once the molecule fits within the receptor, the signal is processed.
Cells then propogate signals by releasing their own redox signaling molecules, to be picked up by other receptors. This downstream effect is known as a signal transduction cascade! It allows messages to be transmitted uniformly across large distances in the body.
Cell signaling is broader and encompasses redox signaling, but both accomplish the same general task of communication between cells! Cell signaling is the process of receiving, processing, and propogating signals. Signals can come from within the cell, outside the cell, or from the environment.
Cell signaling is important because it’s essential to many biological processes. In order to function properly, your body has to convey information between cells, tissues, and organs. For example, cells have to generate appropriate molecules at the appropriate time. And cells have to be quickly alerted of threats and issue directives for repairs!
Source: Nair, A., Chauhan, P., Saha, B., & Kubatzky, K. F. (2019). Conceptual Evolution of Cell Signaling. International journal of molecular sciences, 20(13), 3292. https://doi.org/10.3390/ijms20133292
Redox signaling molecules affect gene expression, because the pathways involved are related!
Gene expression describes which proteins are ultimately made from DNA instructions (sequences known as genes). Gene expression can change depending on how the transcription regulatory pathway responds to signals, like those from redox signaling molecules. When changes must occur, the transcription regulatory pathway alters the way RNA is converted from DNA, thereby altering which proteins are generated.
Since gene expression relates to redox signaling, ASEA commissioned a study in 2016 using gene expression as a key performance indicator for ASEA Redox. The study suggests that over 8 weeks, those who drank ASEA Redox daily experienced a beneficial 20-31% change in 5 genes involved in pathway signaling. For more info, see the [ASEA Redox Gene Science Summary]
Short Answer: Yes! See redox signaling publications and references below for some of our favorite articles.
Long Answer: Redox signaling is a maturing area of research within the fields of cell biology and metabolic studies. A peer-reviewed scientific journal dedicated to understanding the vital impact of redox processes on human health and disease was established in 1999. Estimates put the number of peer-reviewed papers on the topic somewhere in the tens of thousands; they can be found on PubMed.gov, the official U.S. research reporting site. Emerging news can be found in a monthly scientific journal – the ARS Discoveries (Antioxidants & Redox Signaling).
About ASEA Redox:
Under normal circumstances, the body produces redox signaling molecules in healthy nanomolar concentrations. But everyone is different, and various factors can effect the body’s supply of redox signaling molecules.
For example, those with chronic granulamatous disease have such low production of redox signaling molecules, that their immune systems are compromised. Epigenetics also affects production. This means that environmental and behaviorial factors can affect levels of redox signaling molecules. Since redox signaling molecules are involved in so many biological processes, underproduction can lead to a variety of adverse consequences that can be difficult to detect or describe.
The ASEA Redox supplement is intended for those who may have low levels of redox signaling molecules.
Sources:
Kietzmann, T., Petry, A., Shvetsova, A., Gerhold, J. M., & Görlach, A. (2017). The epigenetic landscape related to reactive oxygen species formation in the cardiovascular system. British Journal of Pharmacology, 174(12), 1533–1554. https://doi.org/10.1111/bph.13792
O’Neill, S., Brault, J., Stasia, M.-J., & Knaus, U. G. (2015). Genetic disorders coupled to ROS deficiency. Redox Biology, 6, 135–156. https://doi.org/10.1016/j.redox.2015.07.009
Redox signaling molecules are natural products of metabolism, which is how our bodies process fuel. So rest assured, even with a supplement, your body will still produce its own redox signaling molecules!
Definitely! Each of our bodies is different and has specific needs. With the proper nutrition, exercise, and supplements, you can restore and maintain the optimal level of redox signaling molecules, helping you feel more energized and healthier for longer. If you’re unsure of your health status, have multiple health problems, or are pregnant, speak with your doctor before starting a new supplement regimen. Working with your doctor ahead of time is a good way to determine a program that’s right for you.
ASEA is the first and only source of commercial, stabilized, active redox signaling molecules. The technology behind this is a patented process, involving the reorganization of Na, Cl, H, and O molecules from refined salt and deionized water. The molecular engineering process contains over 30 steps spanning 3 days. The products are then certified to contain redox signaling molecules by multiple third party laboratories!
Since ASEA Redox is classified as a dietary supplement, the FDA offers regulations rather than approval. This means that the FDA issues guidelines for production that ASEA rigorously follows.
ASEA’s production center is certified by NSF International – a global public health and safety organization that provides food safety and quality assurance services across all food supply chain sectors. It is also GMP (Good Manufacturing Practices) compliant. This certification confirms that ASEA’s products comply fully with the regulations set forth by the FDA, as they relate to the production and testing of dietary supplements, with specific standards for safety, quality, and performance.
As a company, ASEA cares deeply about following the guidelines set forth by the FDA and always makes sure to stay up to date with any changes in the regulations or manufacturing practices.
If you're interested in science, there's more...
Continue below for a Redox Overview of relevant terms, and key redox concepts. Check out Redox Homeostasis and Altering ROS Balance to learn about the relationship between ROS and Antioxidants.
Redox Overview
Breaking down redox biology, from the big picture to the specifics
Fundamentals of Redox
Redox — The scientific shorthand for reduction-oxidation
Reduction-Oxidation — A chemical reaction common in biological processes, involving the transfer of electrons from one atom to another. When a redox reaction occurs, atoms become bonded as molecules.
Reduction — When an atom gains electrons
Oxidation — When an atom loses electrons
Reducers (reducing agents) — Substances that cause another substance to gain electrons. They do this by donating their own electrons (thus becoming oxidized). Therefore reducers are also called electron-donors.
Oxidants (oxidizing agents) — Substances that cause another substance to lose electrons. They do this by removing electrons from another substance and incorporating them (thus becoming reduced). Therefore oxidants are also known as electron-acceptors.
※ Oxygen is an oxidant, but the term includes other substances because of similarities to the way oxygen often behaves in chemical reactions.
Fundamentals of Biology
Metabolism — How we process fuel for our bodies! These are chemical reactions that convert energy stored in food into energy usable for cells. Meanwhile, food is also broken down into smaller components that become building blocks for compounds essential to life, such as carbohydrates, proteins, lipids, and nucleic acids. Lastly, any waste products of metabolism are then eliminated as part of the process.
Cellular Respiration — A set of metabolic redox reactions that uses oxygen to break down food into smaller components, generating a large amount of energy in the form of ATP (adenosine triphosphate). This is a primary way to fuel cellular activities.
Biological Pathway — Interactions between molecules within a cell that enable changes or production of new molecules. The main biological pathways are the metabolic pathway, the transcription regulatory pathway, and the signal transduction pathway.
Cell Signaling Pathways — Involves both the transcription regulatory pathway and the signal transduction pathway. Also known as cellular communication, these are biological pathways that enable cells to receive signals through receptors, process signals, and then propogate those signals. Signals can come from within the body or from the environment.
※ The transcription regulatory pathway allows cells to respond to a variety of signals by altering the way it converts DNA to RNA, thereby altering the way genes can be expressed.
Gene Expression determines what encoded info becomes functional products, such as protein.
Enzymes are important proteins that catalyze/accelerate the rates of chemical reactions, so affecting the gene expression of enzymes enables the body to adapt to changes from a genetic level.
Epigenetics describes how behavioral and environmental factors can affect gene expression without changing the DNA sequence itself.
※ The signal transduction pathway involves converting (transducting) all signals received by the receptors into chemical signals capable of activating channels or triggering second messenger systems.
Second Messenger System — Molecules within a cell that amplify signals initially received from outside the cell (from the first messengers). Second messengers amplify signals by propogating them to other cells in a signal transduction cascade. This downstream effect allows messages to be transmitted across large distances, enabling uniform responses and physiological changes.
Redox Signaling Molecules — These are reactive oxygen species (ROS) molecules (notably, H2O2) that act as second messengers for cell signaling, and pathway activators for numerous biological functions.
Redox Biology
Reactive Oxygen Species (ROS) — These molecules are naturally formed in the body from metabolizing oxygen through redox reactions. The most common species include superoxide (O2-), hydroxyl radical (OH), and hydrogen peroxide (H2O2), which is the most significant molecule for redox cell signaling. Under normal, healthy conditions ROS are produced and eliminated in balanced concentrations. However various factors could disrupt ROS levels, and different concentrations of ROS yield different health effects:
※ Reduced concentration: Since H2O2 is essential for activating pathways and propogating signals, diminished levels of ROS inhibit cellular communication and impair bodily functions
※ Extreme high concentration: But because oxygen is very a reactive element, high levels of ROS can disrupt biological systems by oxidizing components unintentionally, causing a type of cell damage known as oxidative stress
※ Slightly elevated concentration: Thus the sweet spot for optimal functioning is a slightly elevated level of ROS, allowing proper pathway activation and cell signaling, without potential oxidative harm. The way our bodies mitigate oxidative stress is by counterbalancing ROS with antioxidants. Your health depends on a balance of both!
Oxidative Stress — A type of cell/tissue damage that results from extreme concentrations of unstable peroxides and free radicals, of which some ROS (especially O2 and OH) are a subspecies. It reflects an imbalance such that there are too many reactive molecules interferring with body systems, incorrectly binding to proteins, lipids, breaking strands in DNA, and interrupting cell signaling. Antioxidants are necessary to balance out oxidants.
Antioxidants — Substances that inhibit oxidation. These can be industrial, dietary (such as vitamins A, C, E), or cellular compounds like glutathione, that prevent oxidative stress by deactivating ROS. Your body has a natural supply of antioxidants, similar to ROS, but of course the balance can be upset. High concentrations of antioxidants means too many ROS molecules are deactivated, resulting in depleted concentrations and impaired signaling.
Redox Homeostasis — The proper balance of ROS and antioxidants, so that redox signaling molecules can do their vital work without negative health risks
NADPH Oxidase — A white blood cell enzyme that serves as one of the primary generators of ROS. It supports immune function by killing bacteria in a sudden release of ROS known as a respiratory burst
Respiratory Burst — A sudden release of ROS for immune, cell signaling, and reproductive purposes
Redox Signaling Molecules & Antioxidants
Redox Homeostasis: Finding the optimal level of ROS
Ultimately it’s about maintaining an equilibrium! Different concentrations of ROS/antioxidants can yield opposite health effects. And redox homeostasis involves finding that balance, to maximize the benefits of cell signaling, without adverse consequence. [10]
Under normal, healthy conditions, ROS (and subsequently redox signaling molecules) exist within cells in nanomolar concentrations. The amount of ROS present is regulated, such that they’re usually balanced out by their molecular counterparts, known as antioxidants. [11]
Because ROS can be reactive, antioxidants are naturally produced to scavenge excess ROS, to neutralize the risk of unintentional interactions with molecules that are important to other biological systems. Too many system disruptions from extreme levels of ROS can have negative results, leading to a type of cell damage known as oxidative stress. But on the other hand, redox signaling molecules are essential to cell survival and cell communication; enough ROS is needed for pathway activation and proper immune function. [1]
Research compiled in this [8] review article outlines how ROS concentrations affect different systems, using 1) cell progression, 2) immune response, and 3) aging as an example.
Reduced Levels of ROS — impaired cell signaling: weakened immunity and accelerated aging
1) insufficient levels of ROS means signal pathways responsible for cell growth, survival, and proliferation remain unactivated
2) immune responses cannot activate without ROS, leading to immunosuppression
3) stem cells do not receive signals necessary for self-renewal and differentiation. tissues are unable to regenerate, leading to accelerated aging
Elevated levels of ROS — optimal for cell signaling and biological function!
1) H2O2 activates pathways, enabling functional metabolism and the production of new blood vessels (angiogenesis). cells are able to fully develop, sustain themselves, reproduce and regenerate
2) sufficient amounts of ROS allow them to act as second messengers for immune cells, signaling macrophages (white blood cells) to fight pathogens such as bacteria, and activating tissue repair pathways as part of the inflammatory response
3) moderate ROS activates stress pathways that slow down the degeneration of tissue, and slow down the natural aging process, possibly increasing longevity. signaling enables damaged cells to be removed. sufficient ROS allows stem cells to maintain their population while also differentiating into new types of necessary tissues
Excessive high levels of ROS — potential for cell damage from oxidative stress
1) high levels of ROS can signal for uncontrolled cell growth, contributing to certain types of cancers, that then produce excessive amounts of antioxidants, further disrupting redox balance
2) immune system becomes hyperactivated from continuous signaling for immune cells. because the inflammatory response is the standard procedure to deal with pathogens, the body can become overly inflammed, developing automimmunity and tissue damage
3) hyper-signaling can cause stem cells to over-proliferate and become exhausted. stem cells decline in numbers and lose their renewal and differentiation capabilities, leading to premature aging
So what alters the balance of redox signaling molecules?
ROS are primarily generated from a type of metabolism known as mitochondrial respiration, and by a type of white blood immune cell enzyme called NADPH oxidase (NOX). Changes to these systems therefore modulates the production of ROS.
Overproduction of ROS
As of now, research is still uncovering what factors affect mitochondrial respiration and NADPH oxidase. Historically, research fixated on oxidative stress as a theory of aging, with most studies examining the overproduction of ROS from external (exogenous) sources. [9] Some studies found that oxidative stress could be induced by exposure to ozone pollution, UV/gamma/X ray radiation, and pesticides, as well as cigarette smoking, certain drugs, and unhealthy high-carb high-fat diet patterns. [4]
Underproduction of ROS
However, experimental results within the last couple decades have revealed inconsistencies to the oxidative stress theory of aging. Researchers are now shifting focus to underproduction of ROS, and fluctuations from internal (endogenous) sources. [7] Scientists investigating chronic granulamatous disease discovered that those afflicted have mutations in the genes encoding NADPH oxidase, causing them to be deficient in ROS. Their white blood cells are unable to release ROS in a respiratory burst, so they remain susceptible to infection. [5] These mutations were always thought to be inherited, but lately emerging research suggests that epigenetics could affect ROS levels. [2] Mitochondria, NOX, and also antioxidant systems can be epigenetically regulated. This means that behaviors and external environment could also affect ROS deficiency.
New! ASEA Redox NRF2 Pathway Study
Studies conducted by the University of Bath, and Western Sydney University suggested that cells treated with redox signaling molecules increased NRF2 pathway activation, without comprising cell viability.
The NRF2 pathway regulates the expression of antioxidant proteins that protect against oxidative stress.
References
- Bardaweel, S. K., Gul, M., Alzweiri, M., Ishaqat, A., ALSalamat, H. A., & Bashatwah, R. M. (2018). Reactive oxygen species: The dual role in physiological and pathological conditions of the human body. The Eurasian Journal of Medicine, 50(3), 193–201. https://doi.org/10.5152/eurasianjmed.2018.17397
- Kietzmann, T., Petry, A., Shvetsova, A., Gerhold, J. M., & Görlach, A. (2017). The epigenetic landscape related to reactive oxygen species formation in the cardiovascular system. British Journal of Pharmacology, 174(12), 1533–1554. https://doi.org/10.1111/bph.13792
- Lennicke, C., & Cochemé, H. M. (2021). Redox metabolism: Ros as specific molecular regulators of cell signaling and function. Molecular Cell, 81(18), 3691–3707. https://doi.org/10.1016/j.molcel.2021.08.018
- Miazek, K., Beton, K., Śliwińska, A., & Brożek-Płuska, B. (2022). The effect of β-carotene, tocopherols and ascorbic acid as anti-oxidant molecules on human and animal in vitro/in vivo studies: A review of research design and analytical techniques used. Biomolecules, 12(8), 1087. https://doi.org/10.3390/biom12081087
- O’Neill, S., Brault, J., Stasia, M.-J., & Knaus, U. G. (2015). Genetic disorders coupled to ROS deficiency. Redox Biology, 6, 135–156. https://doi.org/10.1016/j.redox.2015.07.009
- Paravicini, T. M., & Touyz, R. M. (2006). Redox signaling in hypertension. Cardiovascular Research, 71(2), 247–258. https://doi.org/10.1016/j.cardiores.2006.05.001
- Roy, J., Galano, J., Durand, T., Le Guennec, J., & Chung‐Yung Lee, J. (2017). Physiological role of reactive oxygen species as promoters of natural defenses. The FASEB Journal, 31(9), 3729–3745. https://doi.org/10.1096/fj.201700170r
- Schieber, M., & Chandel, N. S. (2014). Ros function in redox signaling and oxidative stress. Current Biology, 24(10), R453–R462. https://doi.org/10.1016/j.cub.2014.03.034
- Shields, H. J., Traa, A., & Van Raamsdonk, J. M. (2021). Beneficial and detrimental effects of reactive oxygen species on lifespan: A comprehensive review of comparative and experimental studies. Frontiers in Cell and Developmental Biology, 9, 1–27. https://doi.org/10.3389/fcell.2021.628157
- Sies, H. (2021). Oxidative eustress: On constant alert for redox homeostasis. Redox Biology, 41, 101867. https://doi.org/10.1016/j.redox.2021.101867
- Sinenko, S. A., Starkova, T. Yu., Kuzmin, A. A., & Tomilin, A. N. (2021). Physiological signaling functions of reactive oxygen species in stem cells: From flies to man. Frontiers in Cell and Developmental Biology, 9, 1–21. https://doi.org/10.3389/fcell.2021.714370
- Turpaev, K. T. (2002). Reactive Oxygen Species and Regulation of Gene Expression. Biochemistry (Moscow), 67(3), 281–292. https://doi.org/10.1023/a:1014819832003