A blueprint for choosing the right fish oil supplement — filled with specific recommendations, guidelines for interpreting testing data, and dosage protocols.
Dr. Rhonda Patrick makes her third appearance on the Joe Rogan Experience.
A few of the topics and studies mentioned in this episode include...
Lactate can build up in the brain during hypoxic events following trauma, causing cell death. Resource article.
Traumatic brain injury increases risk of developing neurodegenerative diseases such as Alzheimer’s. Review.
Repeated traumatic brain injury has cumulative neuroinflammatory effects in the brain over years, including amyloid-beta plaque and tau tangle formation. Study.
A variant of the APOE gene increases risk of developing Alzheimer’s disease as much as 15-fold. Study.
During sleep, amyloid-beta is cleared from the brain via the glymphatic system.
Endotoxin from human gut bacteria causes learning and memory deficits and depressive symptoms. Study.
Obese children and adults have delayed response to micronutrient-rich CHORI-bar supplementation.
Liposomal glutathione bypasses cellular transport mechanisms to increase heart, brain, and liver glutathione levels. Study.
Topical application of glutathione reduced inflammation and cell death after brain injury in mice. Study.
Curcumin from turmeric induces expression of glutathione-related genes and blunts the pro-inflammatory cascade. Study.
Piperine from black pepper increases the bioavailability of curcumin. Study.
Aromatic turmerone from turmeric repairs damage to the brain by inducing neural stem cell proliferation. Study.
Decreased sense of smell is a predictor of mild cognitive impairment and Alzheimer's disease. Study.
Growth factors from the blood of young mice stimulates stem cell proliferation in the brain and muscles of older mice. Study.
Variants of serotonin-related genes modulate behaviors are associated with personality disorders, impulsivity, and childhood ADHD. Study.
After a single dose of a selective serotonin reuptake inhibitor (SSRI), people become more averse to harming others. Study.
Serotonin is released in the brains of mice pups when nurtured by their mothers, which induces epigenetic changes that increase glucocorticoid receptor transcription. Study.
Vasopressin influences pair bonding in monogamous prairie voles. Study.
Genetic variants in the vasopressin receptor gene influence pair bonding behavior in humans. Study.
When female mice are deprived of cuddling, they become more promiscuous. Study.
The omega-3 fatty acid eicosapentaenoic acid (EPA) modulates mental health. Review paper.
The differences between different omega-3 fatty acid supplement forms are described in Rhonda’s video: The Phospholipid Brain-DHA Advantage.
Mfsd2a is a transporter for the phospholipid form of the omega-3 fatty acid docosahexaenoic acid (DHA). Study.
Alpha-lipoic acid reversed brain aging in rats. Study.
Dietary influences on the conversion of nitrates to nitrites and nitric oxide. Study
The potential therapeutic effects of THC on Alzheimer's disease. Study.
People with higher levels of THC after traumatic brain injury were less likely to die. Study.
Low levels of THC protect mice from traumatic brain injury. Study.
THC protects long-term potentiation receptors, which enhance memory and learning, in mice. Study.
Exercise modulates kynurenine metabolism to protect the brain from neurotoxicity and depression. Study.
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A metabolic process that produces energy using oxygen. During aerobic respiration, the body metabolizes glucose to produce adenosine triphosphate (ATP), which is necessary to power the chemical reactions cells needs to survive. Aerobic respiration is much more efficient and produces ATP much more quickly than anaerobic respiration (respiration without oxygen) because oxygen is an excellent electron acceptor for the chemical reaction. Aerobic respiration takes place in the mitochondria and requires oxygen and glucose, and it produces carbon dioxide, water, and energy.
A naturally occurring substance present in the human body and in some foods. ALA is a powerful antioxidant that amplifies the beneficial effects of other antioxidants in the body such as glutathione and coenzyme Q10. It also participates in metabolism by helping to protect mitochondria from oxidative stress, thus ensuring that energy production in the body remains efficient. Some research suggests that ALA may be useful for treating cataracts, liver disease, and some complications of diabetes such as neuropathy.
A neurodegenerative disorder characterized by progressive memory loss, spatial disorientation, cognitive dysfunction, and behavioral changes. The pathological hallmarks of Alzheimer's disease include amyloid-beta plaques, tau tangles, and reduced brain glucose uptake. Most cases of Alzheimer's disease do not run in families and are described as "sporadic." The primary risk factor for sporadic Alzheimer's disease is aging, with prevalence roughly doubling every five years after age 65. Roughly one-third of people aged 85 and older have Alzheimer's. The major genetic risk factor for Alzheimer's is a variant in the apolipoprotein E (APOE) gene called APOE4.
An area of the brain located close to the hippocampus, in the frontal portion of the temporal lobe. The amygdala governs our responses to fear, arousal, and emotional stimulation. Poor sleep increases activity within the amygdala.
A toxic 42 amino acid peptide that aggregates and forms plaques in the brain with age. Amyloid-beta is associated with Alzheimer's disease, a progressive neurodegenerative disease that can occur in middle or old age and is the most common cause of dementia. Heat shock proteins have been shown to inhibit the early aggregation of amyloid beta 42 and reduce amyloid beta plaque toxicity [1].
One of three common genetic variants of the APOE (apolipoprotein E) gene. The APOE4 allele, which is present in approximately 10-15% of people, increases the risk of developing Alzheimer's disease and lowers the age of onset. Having one copy of E4 increases risk 2- to 3-fold, while having two copies increases risk as much as 15-fold.
A lipoprotein produced in the liver and the brain. In the brain, ApoE transports fatty acids and cholesterol to neurons. In the bloodstream, it binds and transports cholesterol, bringing it to tissues and recycling it back to the liver. Approximately 25% of people carry a genetic variant of this lipoprotein called ApoE4, which is associated with higher circulating levels of LDL cholesterol and a 2- to 3-fold increased risk of developing Alzheimer's disease.
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.
The shrinking or wasting away of cells, organs, or tissues that may occur as part of a disease process, trauma, or aging.
A developmental disorder characterized by impaired social interaction, behavioral problems, and poor communication. Autism typically manifests in early childhood and is slightly more common among boys than girls. In clinical trials, sulforaphane, a compound derived from broccoli and broccoli sprouts, reduces the characteristic behaviors associated with autism.
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 wavelength of light emitted from natural and electronic sources. Blue light exposure is associated with improved attention span, reaction time, and mood. However, exposure to blue light outside the normal daytime hours may suppress melatonin secretion, impairing sleep patterns. In addition, blue light contributes to digital eye strain and may increase risk of developing macular degeneration.
Five to ten percent of breast cancers in the U.S. are linked to an inherited gene mutation, BRCA1 and BRCA2 (BReast CAncer genes 1 and 2) are the best-known genes linked to breast cancer. People who have a BRCA1/2 mutation have a greatly increased risk of breast cancer and (for women) ovarian cancer.
A collective term for the various components of Cannabis sativa, also known as marijuana.
A waxy lipid produced primarily in the liver and intestines. Cholesterol can be synthesized endogenously and is present in all the body's cells, where it participates in many physiological functions, including fat metabolism, hormone production, vitamin D synthesis, and cell membrane integrity. Dietary sources of cholesterol include egg yolks, meat, and cheese.
A neurodegenerative disorder associated with repetitive brain trauma, including mild concussion injuries. CTE causes executive dysfunction, memory impairment, depression, suicidal behaviors, apathy, poor impulse control, and eventually dementia. Beyond repetitive brain trauma, the risk factors for CTE remain unknown. The hallmarks of CTE include aggregation and accumulation of hyperphosphorylated tau and transactive response DNA binding protein, or TDP-43. CTE is commonly observed in contact sport athletes and individuals with a history of military combat.
Cooling of the body for therapeutic purposes. Cryotherapy can include the use of products such as ice packs on a localized portion of the body, such as a joint or muscle, or whole body exposure to extremely low temperatures in water or air. Cryotherapy has profound effects on many parts and functions of the body, including the brain, immune system, and metabolism, among others.
An antioxidant compound produced by the plant Curcuma longa, a member of the ginger family. Curcumin exhibits a wide array of beneficial health effects, including anti-inflammatory, anti-cancer, and anti-diabetes properties. It is responsible for the bright yellow pigment of turmeric, a type of spice commonly used in Indian food.
A broad category of small proteins (~5-20 kDa) that are important in cell signaling. Cytokines are short-lived proteins that are released by cells to regulate the function of other cells. Sources of cytokines include macrophages, B lymphocytes, mast cells, endothelial cells, fibroblasts, and various stromal cells. Types of cytokines include chemokines, interferons, interleukins, lymphokines, and tumor necrosis factor.
A general term referring to cognitive decline that interferes with normal daily living. Dementia commonly occurs in older age and is characterized by progressive loss of memory, executive function, and reasoning. Approximately 70 percent of all dementia cases are due to Alzheimer’s disease.
A mood disorder characterized by profound sadness, fatigue, altered sleep and appetite, as well as feelings of guilt or low self-worth. Depression is often accompanied by perturbations in metabolic, hormonal, and immune function. A critical element in the pathophysiology of depression is inflammation. As a result, elevated biomarkers of inflammation, including the proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, are commonly observed in depressed people. Although selective serotonin reuptake inhibitors and cognitive behavioral therapy typically form the first line of treatment for people who have depression, several non-pharmacological adjunct therapies have demonstrated effectiveness in modulating depressive symptoms, including exercise, dietary modification (especially interventions that capitalize on circadian rhythms), meditation, sauna use, and light therapy, among others.
The biological process in which a cell matures and specializes. Differentiation is essential for the development, growth, reproduction, and lifespan of multicellular organisms. Differentiated cells can only express genes that characterize a certain type of cell, such as a liver cell, for example.
An omega-3 fatty acid found in the human brain and the meat of fatty fish. DHA plays a key role in the development of eye and nerve tissues, and is essential for normal brain function in humans. DHA may also reduce the risk of Alzheimer’s disease1 and cardiovascular disease, and may be useful in treating certain inflammatory conditions, such as rheumatoid arthritis. Dietary sources of DHA include krill oil and the meat and roe of salmon, flying fish, and pollock. [1] Patrick, Rhonda P. "Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer’s disease." The FASEB Journal (2018): fj-201801412R.
A type of toxin released when bacteria die. Endotoxins can leak through the intestinal wall and pass directly into the bloodstream. The most common endotoxin is lipopolysaccharide (LPS), a major component of the cell membrane of gram-negative bacteria. If LPS leaks into the bloodstream, it can trigger an acute inflammatory reaction. LPS has been linked with a number of chronic diseases, including Alzheimer’s disease, inflammatory bowel disease (Crohn’s disease or ulcerative colitis), cardiovascular disease, diabetes, obesity, autoimmune disorders (celiac disease, multiple sclerosis, and type 1 diabetes), and psychiatric disorders (anxiety and depression).
Genetic control elicited by factors other than modification of the genetic code found in the sequence of DNA. Epigenetic changes determine which genes are being expressed, which in turn may influence disease risk. Some epigenetic changes are heritable.
A broad class of supportive cells in the central nervous system. Glial cells surround and provide support for and insulation between neurons. Unlike neurons, glial cells do not conduct electrical impulses. Glial cells are the most abundant cell types in the central nervous system, outnumbering neurons by a ratio of roughly 3 to 1. They are generally smaller than neurons, and they lack axons and dendrites. Types of glial cells include oligodendrocytes, astrocytes, ependymal cells, Schwann cells, microglia, and satellite cells.
An antioxidant compound produced by the body’s cells. Glutathione helps prevent damage from oxidative stress caused by the production of reactive oxygen species.
An antioxidant produced within cells that enzymatically reduces hydrogen peroxide to water to limit its harmful effects. Glutathione peroxidase's primary role is to protect cells from oxidative damage, a key factor in many diseases.
An antioxidant produced within cells that converts oxidized glutathione to reduced glutathione. Glutathione reductase is essential for protection against oxidative damage. Oxidative damage is a key factor in many diseases.
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.
A system that clears the brain of metabolites and other waste. The glymphatic system comprises a vast arrangement of interstitial fluid-filled cavities surrounding the small blood vessels that serve the brain. During sleep, these perivascular structures increase in size by more than 60 percent. This allows a “flushing” operation in which waste products can be eliminated. The glymphatic system also facilitates the distribution of essential nutrients such as glucose, lipids, and amino acids, as well as other substances, such as growth factors and neuromodulators.
A circulating lipoprotein that picks up cholesterol in the arteries and deposits it in the liver for reprocessing or excretion. HDL is often referred to as the "good cholesterol."
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.
High blood pressure. Hypertension, defined as a systolic pressure of 130 mm Hg or higher, or a diastolic pressure of 80 mm Hg or higher, is a robust predictor of future incidence of stroke, coronary heart disease, heart attack, heart failure, and cardiovascular-related death. Central to the pathophysiology of hypertension is the loss of arterial compliance, which can have far-reaching effects on multiple organ systems, including the brain and kidneys.
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 peptide hormone secreted by the beta cells of the pancreatic islets cells. Insulin maintains normal blood glucose levels by facilitating the uptake of glucose into cells; regulating carbohydrate, lipid, and protein metabolism; and promoting cell division and growth. Insulin resistance, a characteristic of type 2 diabetes, is a condition in which normal insulin levels do not produce a biological response, which can lead to high blood glucose levels.
A group of signaling proteins made and released by host cells in response to the presence of several pathogens, such as viruses, bacteria, parasites, and tumor cells. Interferons are named for their ability to interfere with viral replication and are critical components of the body's innate immune response to viruses. SARS-CoV-2, the virus that causes COVID-19, impairs the body's interferon response.
A compound produced during the conversion of the amino acid tryptophan to the vitamin niacin (vitamin B3). Kynurenine is pivotal to the tryptophan metabolism pathway because it can change into the neuroprotective agent kynurenic acid or to the neurotoxic agent quinolinic acid, the latter of which has been implicated in many disorders such as stroke, epilepsy, and multiple sclerosis, and in neurodegenerative disorders such as Parkinson's disease, Huntington's, and Alzheimer's disease.
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.
A medical condition characterized by the buildup of lactate in the body and can occur as the result of an underlying acute or chronic medical condition, medication or poisoning.
A group of blood tests that measures the amount of lipids (fats) in a person’s blood. Typical elements of a lipid panel (also known as a lipid profile) include total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels. Increasingly, evidence suggests that blood tests that assess predominant particle size may also be an important factor in interpreting the overall impact of HDL and LDL values.
Large molecules consisting of a lipid and a polysaccharide with an O-antigen outer core. Lipopolysaccharides are found in the outer membrane of Gram-negative bacteria and elicit strong immune responses in animals through pattern recognition conferred by a toll-like receptor known as TLR4. Even a low dose LPS challenge of 0.6 ng/kg body weight given intravenously can induce a profound, if transient, 25-fold and 100-fold increase in plasma IL-6 and TNF-alpha, respectively.[1] Also known as bacterial endotoxin.
Lipid-protein complexes that allow fats to move through the watery environment inside and outside cells. Lipoproteins emulsify the lipid molecules.
A lipid particle that can encapsulate water-soluble substances. Liposomes are commonly used as drug delivery systems because they enhance uptake in the gut and increase bioavailability of the delivered substance.
A carotenoid compound present in many fruits and vegetables. Lutein filters high energy blue light and serves as an antioxidant that quenches and scavenges reactive oxygen species. In humans, lutein accumulates in the lens and the macula, an area of the retina responsible for central and high acuity vision.Lutein consumption is inversely related to eye diseases such as age-related macular degeneration (AMD) and cataracts.
A medical condition that may result in blurred or no vision in the center of the visual field. A combination of genetics and environmental factors that cause oxidative stress, such as smoking and obesity, play a role. Often referred to as “age-related macular degeneration.”
A series of connective tissue membranes that surround the brain and spinal cord. The meninges are separated by cerebrospinal fluid, which acts as a cushion, supporting the brain and protecting it from damage that might be caused by movement or trauma.
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.
Vitamins and minerals that are required by organisms throughout life in small quantities to orchestrate a range of physiological functions. The term micronutrients encompasses vitamins, minerals, essential amino acids, essential fatty acids.
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.
A mucopolysaccharide or glycoprotein that is the chief constituent of mucus secreted by the epithelial cells lining the gut in order to produce a barrier preventing infection by microorganisms inhabiting the gut.
A sulfur-containing amino acid. N-acetylcysteine promotes the body’s production of glutathione, an important antioxidant that helps reduce oxidative damage. It is commonly used for the treatment of acetaminophen overdose and chronic obstructive pulmonary disease. N-acetylcysteine modulates several neurological pathways, including glutamate dysregulation, oxidative stress, and inflammation. It may be useful as an adjunctive therapy for many psychiatric conditions, including PTSD and depression.
The process of forming new neurons. Neurogenesis is essential during embryonic development, but also continues in certain brain regions throughout human lifespan.
The brain's ability to reorganize itself by forming new neural connections throughout life. Neuroplasticity allows the neurons (nerve cells) in the brain to compensate for injury and disease and to adjust their activities in response to new situations or to changes in their environment.
A substance that is detrimental to the nervous system. Neurotoxins damage neurons, interrupting the transmission of signals. They can be found in the environment in both natural and man-made products. The body produces some substances that are neurotoxic. Examples of neurotoxins include lead, alcohol, tetrodotoxin (from pufferfish), and nitric oxide.
A small molecule synthesized by nitric oxide synthase from the amino acid L-arginine. Nitric oxide is a highly reactive signaling molecule that freely diffuses across cell membranes. It regulates a variety of biological functions throughout the body, including vascular tone and blood flow; leukocyte adhesion and platelet aggregation; and mitochondrial oxygen consumption. Abnormalities in vascular nitric oxide production and transport are associated with hypertension, atherosclerosis, diabetes, hypercholesterolemia, and hypertension.
A chemical compound produced in the body through the oxidation of nitric oxide or through a reduction of nitrate by commensal bacteria in the mouth and gut. Nitrites are also obtained in the diet, with roughly 80 percent of dietary nitrates derived from vegetable consumption. Foods rich in nitrites include spinach, celery, beets, and tomatoes, among others. Nitrites are also used as additives to processed meats, such as bacon or sausage. Whereas nitrites in vegetables improve oxygen efficiency and delivery by dilating blood vessels, which is associated with reduced blood pressure, decreased age-related cognitive decline, and enhanced blood flow, nitrites in processed meats convert to nitrosamines, which are associated with increased risk of developing several types of cancer.
Chemical compounds of the chemical structure R1N(-R2)-N=O, that is, a nitroso group bonded to an amine. Approximately 90% of nitrosamine compounds studies were deemed to be carcinogenic. Nitrites, often used as chemical preservatives, readily form nitrosamines. Frying foods can enhance the formation of nitrosamines, while ascorbic acid has been shown to inhibit their formation.
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.
One of four nitrogen-containing molecules that comprise DNA. A nucleotide consists of one of four chemicals, called a “base,” plus one molecule of sugar and one molecule of phosphoric acid. Nucleotides are typically identified by the first letter of their base names: adenine (A), cytosine (C), guanine (G), and thymine (T). They form specific pairs (A with T, and G with C), and their bonds provide the helical structure of the DNA strand.
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.
A chemical reaction in which an atom, molecule, or ion loses one or more electrons. Oxidation of biological molecules is associated with oxidative stress, a key driver of many chronic diseases.
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.
A result of oxidative metabolism, which causes damage to DNA, lipids, proteins, mitochondria, and the cell. Oxidative stress occurs through the process of oxidative phosphorylation (the generation of energy) in mitochondria. It can also result from the generation of hypochlorite during immune activation.
A neurodegenerative disorder that affects the central nervous system. Parkinson’s disease is caused by destruction of nerve cells in the part of the brain called the substantia nigra. It typically manifests later in life and is characterized by tremors and a shuffling gait.
In general, anything that can produce disease. Typically, the term is used to describe an infectious agent such as a virus, bacterium, prion, fungus, or other microorganism.
A class of chemical compounds produced in plants in response to stressors. Polyphenols contribute to the bitterness, astringency, color, flavor, and fragrance of many fruits and vegetables. They often serve as deterrents to insect or herbivore consumption. When consumed in the human diet, polyphenols exert many health benefits and may offer protection against development of cancers, cardiovascular diseases, diabetes, osteoporosis, and neurodegenerative diseases. Dietary sources of polyphenols include grapes, apples, pears, cherries, and berries, which provide as much as 200 to 300 mg polyphenols per 100 grams fresh weight.
The area of the brain located in the front portion of the frontal lobe, just behind the area commonly known as the forehead. The prefrontal cortex is involved in a variety of higher cognitive functions and behaviors such as executive function and expression of appropriate social behavior.
A group of lipid-signaling molecules that have diverse hormone-like effects. Prostaglandins play roles in inflammation, vasoconstriction or vasodilation, aggregation or disaggregation of platelets, calcium movement, cell growth, and thermoregulation. Prostaglandins are produced in many places throughout the human body.
A bioactive compound found in many edible plants. Quercetin demonstrates a wide range of health-promoting characteristics, including antioxidant, anti-inflammatory, and anti-cancer properties. It scavenges reactive oxygen and nitrogen species, inhibits activation of the proinflammatory molecule nuclear factor kappa B (NF-κB), and downregulates the inflammatory response of macrophages. When used in conjunction with the chemotherapy drug dasatinib, quercetin shows promise as a senolytic (anti-aging) compound, effectively clearing senescent cells and promoting improvements in a variety of age-related diseases. Dietary sources of quercetin include onions (most abundant), apples, berries, leafy vegetables, herbs, spices, legumes, tea, and cocoa.
A compound produced during the metabolism of the amino acid, tryptophan. Quinolinic acid is a neurotoxin released by activated macrophages. It may play roles in inflammation and neurodegenerative disorders. Elevated quinolinic acid levels are correlated with the severity of neuropsychological deficits in people who have AIDS.
Nitrogen-containing chemically-reactive molecules generated by the immune system. RNS are produced in animals when nitric oxide reacts with superoxide to form peroxynitrite. They can damage cellular components, including lipids, proteins, mitochondria, and DNA. Examples of RNS include nitric oxide, peroxynitrite, and nitrogen dioxide.
A related byproduct, reactive oxygen species, is generated by oxidative phosphorylation and immune activation. Examples of ROS include: peroxides, superoxide, hydroxyl radical, and singlet oxygen.
The two species are often collectively referred to as ROS/RNS. Preventing and efficiently repairing damage from RNS (nitrosative stress) and ROS (oxidative stress) are among the key challenges our cells face in their fight against diseases of aging, including cancer.
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 polyphenolic compound produced in plants in response to injury or pathogenic attack from bacteria or fungi. Resveratrol exerts a diverse array of biological effects, including antitumor, antioxidant, antiviral, and hormonal activities. It activates sirtuin 1 (SIRT1), an enzyme that deacetylates proteins and contributes to cellular regulation (including autophagy). Dietary sources of resveratrol include grapes, blueberries, raspberries, and mulberries.
Resveratrol Autophagy ↑ Deacetylases (especially SIRT1) → ↓ Protein Acetylation → Autophagy
A small molecule that functions as both a neurotransmitter and a hormone. Serotonin is produced in the brain and gut and facilitates the bidirectional communication between the two. It regulates many physiological functions, including sleep, appetite, mood, thermoregulation, and others. Many antidepressants are selective serotonin reuptake inhibitors (SSRIs), which work by preventing the reabsorption of serotonin, thereby increasing extracellular levels of the hormone.
A change in one nucleotide DNA sequence in a gene that may or may not alter the function of the gene. SNPs, commonly called "snips," can affect phenotype such as hair and eye color, but they can also affect a person's disease risk, absorption and metabolism of nutrients, and much more. SNPs differ from mutations in terms of their frequency within a population: SNPs are detectable in >1 percent of the population, while mutations are detectable in <1 percent.
A type of reactive oxygen species. Singlet oxygen is generated in cells as a result of exposure to UV light or visible irradiation. It induces damage in cellular proteins, keratinocytes (a type of skin cell), and DNA.
A class of drugs that lower blood cholesterol levels by blocking the production of an enzyme in the liver called hydroxy-methylglutaryl-coenzyme A reductase (HMG-CoA reductase). Taking statins may reduce the risk of cardiovascular disease in some people. Although statins are generally well tolerated, as many as 10 – 20 percent of people taking the drugs experience complications, including myopathy (muscle damage), liver damage, and cognitive problems, including issues with forgetfulness, memory loss, and confusion.
A cell that has the potential to develop into different types of cells in the body. Stem cells are undifferentiated, so they cannot do specific functions in the body. Instead, they have the potential to become specialized cells, such as muscle cells, blood cells, and brain cells. As such, they serve as a repair system for the body. Stem cells can divide and renew themselves over a long time. In 2006, scientists reverted somatic cells into stem cells by introducing Oct4, Sox2, Klf4, and cMyc (OSKM), known as Yamanaka factors.[1]
The junction between one neuron and another or a gland or muscle cell. Synapses are critical elements in the transmission of nerve signals. Their formation is necessary for the establishment and maintenance of the brain’s neuronal network and the precision of its circuitry.
A microtubule-bound protein that forms the neurofibrillary "tau tangles" associated with Alzheimer's disease. Tau tangles disrupt transport of metabolites, lipids, and mitochondria across a neuron to the synapse where neurotransmission occurs. Diminished slow-wave sleep is associated with higher levels of tau in the brain. Elevated tau is a sign of Alzheimer's disease and has been linked to cognitive decline.
Abnormal aggregates of hyperphosphorylated tau, a protein found in the brain. Tau tangles are associated with traumatic brain injury and chronic traumatic encephalopathy and are one of the defining characteristics of Alzheimer’s disease. They inhibit normal brain function, and the degree of cognitive impairment in diseases such as Alzheimer’s is significantly correlated with their presence.
The primary psychoactive substance present in the leaves of the marijuana (cannabis) plant. THC alters the functioning of the hippocampus and orbitofrontal cortex, leading to altered perception and changes in cognition, such as short-term memory impairment. THC’s chemical structure is similar to the brain’s endogenous cannabinoid anandamide, allowing it to bind to anandamide receptors to elicit its effects.
A protein that binds to specific DNA sequences, thereby controlling the rate of transcription of genetic information from DNA to messenger RNA. A defining feature of transcription factors is that they contain one or more DNA-binding domains, which attach to specific sequences of DNA adjacent to the genes that they regulate.
An animal that has had its genome altered through the use of genetic engineering techniques, usually during early embryonic stages. Transgenic techniques are routinely used to introduce human disease genes or other genes of interest into strains of laboratory animals in order to study the function or pathology involved with a particular gene.
Damage to the brain caused by a sudden blow, penetrating injury, or lack of oxygen, ranging from mild to severe. TBIs can induce a wide range of short- or long-term changes in the brain that affect thinking, sensation, language, personality, and emotion. In addition, TBI may increase the risk for developing epilepsy, Alzheimer’s disease, Parkinson’s disease, and other brain disorders. Nearly 75 percent of TBIs that occur each year are concussions or other forms of mild TBI. Even mild TBIs damage the delicate tissues and blood vessels of the brain and can result in altered brain function that can persist for days, weeks, or months. Approximately 15 percent of concussed athletes experience symptoms as long as one year after their injury, a condition called persistent post-concussion syndrome, or PPCS, typically after returning to play too quickly.
A molecule composed of a glycerol molecule bound to three fatty acids. Triglycerides are the primary component of very-low-density lipoproteins (VLDL). They serve as a source of energy. Triglycerides are metabolized in the intestine, absorbed by intestinal cells, and combined with cholesterol and proteins to form chylomicrons, which are transported in lymph to the bloodstream.
An essential amino acid. Tryptophan plays key roles in the biosynthesis of proteins and is a precursor to several molecules with physiological significance, including melatonin, niacin, and the neurotransmitter serotonin. Inflammation causes tryptophan to be reallocated from serotonin synthesis to that of kynurenine, which then converts to the neurotoxin quinolinic acid, leading to depression. Dietary sources of tryptophan include most protein-based foods, such as meat, beans, or nuts.
A rhizomatous herbaceous perennial plant of the ginger family that grows wild in the forests of South and Southeast Asia. Turmeric’s strong antioxidant and anti-inflammatory properties are attributed to its high concentration of curcumin. After being boiled and dried out, turmeric has a golden-orange color.
A pituitary hormone that acts to promote the retention of water by the kidneys and increase blood pressure.
A potent water-soluble antioxidant found in citrus fruits. Vitamin C is an essential nutrient involved in tissue repair, neurotransmission, and immune system function. Also known as ascorbic acid.
A fat-soluble vitamin stored in the liver and fatty tissues. Vitamin D plays key roles in several physiological processes, such as the regulation of blood pressure, calcium homeostasis, immune function, and the regulation of cell growth. In the skin, vitamin D decreases proliferation and enhances differentiation. Vitamin D synthesis begins when 7-dehydrocholesterol, which is found primarily in the skin’s epidermal layer, reacts to ultraviolet light and converts to vitamin D. Subsequent processes convert D to calcitriol, the active form of the vitamin. Vitamin D can be obtained from dietary sources, too, such as salmon, mushrooms, and many fortified foods.
A fat-soluble vitamin. Vitamin E is the collective name for a group of eight fat-soluble compounds (alpha-, beta-, gamma-, & delta-tocopherol and alpha-, beta-, gamma-, & delta-tocotrienol) with distinctive antioxidant activities. Of these eight, only alpha- (α-) tocopherol meets human requirements. Vitamin E serves as an antioxidant that breaks the chain reaction formation of reactive free radicals. In doing so it becomes oxidized and loses its antioxidant capacity. Vitamin E also protects LDL from oxidation and maintains the integrity of cell membranes throughout the body. Dietary sources of vitamin E include nuts, seeds, eggs, and fatty fish, such as salmon.
A type of fat-soluble vitamin that participates in blood clotting and bone metabolism. Naturally occurring forms of vitamin K include phylloquinone (vitamin K1) and a family of molecules called menaquinones (vitamin K2). Vitamin K1 is synthesized by plants and is the major form present in the diet. Vitamin K2 molecules are synthesized by the gut microbiota and found in fermented foods and some animal products (especially liver). The body has limited vitamin K storage capacity, so the body recycles it in a vitamin K redox cycle and reuses it multiple times.
A foreign substance that is introduced into the body from the environment and is subsequently metabolized. Xenobiotics can exert multiple effects (good or bad) on the body by disrupting or interacting with cellular communication pathways that regulate growth, development, and normal physiological function. They are subject to extensive biotransformation in the human body via Phase 1 and Phase 2 metabolism, with a goal toward elimination. Examples of xenobiotics include drugs, pollutants, and plant-based dietary compounds.
A carotenoid compound present in plants, algae, and bacteria. Zeaxanthin is an antioxidant that quenches and scavenges reactive oxygen species. It preferentially accumulates in the lens and macula of the eye. Some observational studies demonstrate that high intake of zeaxanthin and lutein (also a carotenoid) is associated with a 20 percent reduced risk of developing cataracts and up to 40 percent reduced risk of developing age-related macular degeneration.
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