A molecule that inhibits oxidative damage to DNA, proteins, and lipids in cells. Oxidative damage plays a role in the aging process, cancer, and neurodegeneration. Many vitamins and plant-based compounds are antioxidants.

Star-shaped cells found in the brain and spinal cord. Astrocytes facilitate neurotransmission, provide nutrients to neurons, maintain neuronal ion balance, and support the blood-brain barrier. Astrocytes also play a role in the repair and scarring process of the brain and spinal cord following traumatic injuries.

A chemical produced in the liver via the breakdown of fatty acids. Beta-hydroxybutyrate is a type of ketone body. It can be used to produce energy inside the mitochondria and acts as a signaling molecule that alters gene expression by inhibiting a class of enzymes known as histone deacetylases.

A highly selective semi-permeable barrier in the brain made up of endothelial cells connected by tight junctions. The blood-brain barrier separates the circulating blood from the brain's extracellular fluid in the central nervous system. Whereas water, lipid-soluble molecules, and some gases can pass through the blood-brain barrier via passive diffusion, molecules such as glucose and amino acids that are crucial to neural function enter via selective transport. The barrier prevents the entry of lipophilic substances that may be neurotoxic via an active transport mechanism.

A survival mechanism the brain relies on during starvation. Glucose sparing occurs when the body utilizes fatty acids as its primary fuel and produces ketone bodies. The ketone bodies cross the blood-brain barrier and are used instead of glucose, thereby “sparing” glucose for use in other metabolic pathways, such as the pentose-phosphate pathway, which produces NADPH. NADPH is essential for the production of glutathione, one of the major antioxidants used in the body and brain.

A series of enzyme-dependent reactions that breaks down glucose. Glycolysis converts glucose into pyruvate, releasing energy and producing ATP and NADH. In humans, glycolysis occurs in the cytosol and does not require oxygen.

Biological responses to low-dose exposures to toxins or other stressors such as exercise, heat, cold, fasting, and xenohormetics. Hormetic responses are generally favorable and elicit a wide array of protective mechanisms. Examples of xenohormetic substances include plant polyphenols – molecules that plants produce in response to stress. Some evidence suggests plant polyphenols may have longevity-conferring effects when consumed in the diet.

Abnormally low blood glucose. Hypoglycemia can occur due to low glycogen stores, diabetes medications, or other drugs. Maternal alcohol consumption can cause hypoglycemia in breastfed infants. Symptoms of hypoglycemia include confusion, heart palpitations, shakiness, and anxiety.

Condition in which the body or a region of the body is deprived of adequate oxygen supply. Hypoxia may be classified as either generalized, affecting the whole body, or local, affecting a region of the body.

A diet that causes the body to oxidize fat to produce ketones for energy. A ketogenic diet is low in carbohydrates and high in proteins and fats. For many years, the ketogenic diet has been used in the clinical setting to reduce seizures in children. It is currently being investigated for the treatment of traumatic brain injury, Alzheimer's disease, weight loss, and cancer.

Molecules (often simply called “ketones”) produced by the liver during the breakdown of fatty acids. Ketone production occurs during periods of low food intake (fasting), carbohydrate restrictive diets, starvation, or prolonged intense exercise. There are three types of ketone bodies: acetoacetate, beta-hydroxybutyrate, and acetone. Ketone bodies are readily used as energy by a diverse array of cell types, including neurons.

Lactate is thought to participate in a sort of "lactate shuttle" where, after being produced in muscle from exercise, it is transported in to tissues like the heart, and brain, where it is used as an energy source. Lactate is one of many molecules that falls under a loose group of molecules referred to as exerkines, a broad group of exercise-induced hormonal-like factors. Evidence suggests that lactate is the preferred fuel of the brain. Additionally, rodent studies suggest that lactate mediates some of the benefits of exercise on learning and memory via inducing neuronal brain-derived neurotrophic factor (BDNF) expression.^[1] In clinical studies, lactate shows promise as a treatment for inflammatory conditions including traumatic brain injury and as a means to deliver fuel to working muscles.

Lactate that is produced from an oxygen-independent metabolic pathway (glycolysis) is shuttled to various tissues including muscle, heart, and brain, where it is used as a substrate for oxygen-dependent energy production.

The thousands of biochemical processes that run all of the various cellular processes that produce energy. Since energy generation is so fundamental to all other processes, in some cases the word metabolism may refer more broadly to the sum of all chemical reactions in the cell.

Tiny organelles inside cells that produce energy in the presence of oxygen. Mitochondria are referred to as the "powerhouses of the cell" because of their role in the production of ATP (adenosine triphosphate). Mitochondria are continuously undergoing a process of self-renewal known as mitophagy in order to repair damage that occurs during their energy-generating activities.

The process by which new mitochondria are made inside cells. Many factors can activate mitochondrial biogenesis including exercise, cold shock, heat shock, fasting, and ketones. Mitochondrial biogenesis is regulated by the transcription factor peroxisome proliferator-activated receptor gamma coactivator 1-alpha, or PGC-1α.

A protein typically present in the cytoplasm of mammalian cells. Nrf2 can relocate to the nucleus where it regulates the expression of hundreds of antioxidant and stress response proteins that protect against oxidative damage triggered by injury and inflammation. One of the most well-known naturally-occurring inducers of Nrf2 is sulforaphane, a compound derived from cruciferous vegetables such as broccoli.

Highly reactive molecules that have the ability to oxidize other molecules and cause them to lose electrons. Common oxidants are oxygen, hydrogen peroxide, and superoxide anion.

The process of generating energy that occurs when mitochondria couple oxygen with electrons that have been derived from different food sources including glucose, fatty acids, and amino acids.

An alternate pathway for the oxidation of glucose. The pentose phosphate pathway parallels glycolysis, but does not require or produce ATP; rather, it produces NADPH, which is necessary to create the cellular antioxidant glutathione. Like glycolysis, the pentose phosphate pathway occurs in the cytoplasm.

Oxygen-containing chemically-reactive molecules generated by oxidative phosphorylation and immune activation. ROS can damage cellular components, including lipids, proteins, mitochondria, and DNA. Examples of ROS include: peroxides, superoxide, hydroxyl radical, and singlet oxygen.

A related byproduct, reactive nitrogen species, is also produced naturally by the immune system. Examples of RNS include nitric oxide, peroxynitrite, and nitrogen dioxide.

The two species are often collectively referred to as ROS/RNS. Preventing and efficiently repairing damage from ROS (oxidative stress) and RNS (nitrosative stress) are among the key challenges our cells face in their fight against diseases of aging, including cancer.

A chemical reaction in which an atom, molecule, or ion gains one or more electrons.

A fat-soluble compound that is present inside the inner-mitochondrial membrane of cells. It plays a role in aerobic cellular respiration which produces energy in the presence of oxygen. The heart, liver, and kidney have the highest CoQ10 concentrations.