The death rate from all causes of death for a population in a given time period.

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.

A test used in laboratory medicine, pharmacology, environmental biology, and molecular biology to determine the content or quality of specific components.

A disease characterized by the deposition of fatty plaques on the inner walls of arteries. Something is said to be atherogenic when it promotes the formation of fatty plaques in the arteries. Atherosclerosis causes coronary artery disease.

An immune disorder characterized by an immune response to and subsequent destruction of the body’s own tissue. The causes of autoimmune diseases are not known, but a growing body of evidence suggests they may be due to interactions between genetic and environmental factors. Autoimmune diseases affect approximately 7 percent of the population in the United States and are more common in women than in men. Examples include type 1 diabetes, Hashimoto’s thyroiditis, lupus, and multiple sclerosis.

The extent and rate at which drugs or other substances, such as plant-based dietary compounds, enter the body’s circulation. Bioavailability is influenced by a variety of factors, including dose, the presence of other foods or substances, and interindividual differences in metabolism due to gut absorptive surface and commensal microbial populations.

Bacteria that are beneficial or at least not harmful to the host, in contrast to pathogenic bacteria where the host derives no benefit and is actively harmed from the relationship. Roughly 100 trillion commensal bacteria live in the human gut. The term commensal comes from Latin and literally means “eating at the same table.”

A steroid hormone that participates in the body’s stress response. Cortisol is a glucocorticoid hormone produced in humans by the adrenal gland. It is released in response to stress and low blood glucose. Chronic elevated cortisol is associated with accelerated aging. It may damage the hippocampus and impair hippocampus-dependent learning and memory in humans.

An infectious disease caused by the novel coronavirus SARS-CoV-2. COVID-19, or coronavirus disease 2019, was first identified in Wuhan, China, in late 2019. The disease manifests primarily as a lower respiratory illness, but it can affect multiple organ systems, including the cardiovascular, neurological, gastrointestinal, and renal systems. Symptoms include fever, cough, fatigue, shortness of breath, and loss of smell and taste. Some infected persons, especially children, are asymptomatic. Severe complications of COVID-19 include pneumonia, sepsis, acute respiratory distress syndrome, kidney failure, multiple organ dysfunction syndrome, and cytokine storm. Treatments currently involve symptom management and supportive care. Mortality varies by country and region, but approximately 6 percent of people living in the United States who are diagnosed with COVID-19 expire.[1] 1

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 hyperinflammatory response to infection. Cytokine storm is characterized by the overproduction of immune cells and pro-inflammatory cytokines. A frequent complication of cytokine storm is multiple organ dysfunction. Cytokine storm is often present in severe cases of COVID-19.

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.

A major contributing factor to aging, cellular senescence, and the development of cancer. Byproducts of both mitochondrial energy production and immune activity are major sources of DNA damage. Additionally, environmental stressors can increase this base level of damage. DNA damage can be mitigated by cellular repair processes; however, the effectiveness of these processes may be influenced by the availability of dietary minerals, such as magnesium, and other dietary components, which are needed for proper function of repair enzymes.

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.

An unhealthy change in the normal bacterial ecology of a part of body, e.g., the intestines or the oral cavity.

A collective term for a group of conditions characterized by itchy or inflamed skin with a rash-like appearance. Seven types of eczema have been identified: atopic dermatitis, contact dermatitis, dyshidrotic eczema, nummular eczema, seborrheic dermatitis, and stasis dermatitis.

An omega-3 fatty acid found in the meat of fatty fish. EPA reduces inflammation in the body and helps counter oxidative stress in cells. It is crucial for modulating behavior and mood and has demonstrated beneficial effects in managing anxiety and depression. EPA may reduce risk of developing certain chronic diseases such as cancer or cardiovascular disease. Dietary sources of EPA include herring, salmon, eel, shrimp and sturgeon.

Any of a group of complex proteins or conjugated proteins that are produced by living cells and act as catalyst in specific biochemical reactions.

Endogenous female sex hormones. Estrogens include estrone, estradiol, and estriol. They promote the development and maintenance of secondary sex characteristics in females. Estrogens regulate the menstrual cycle and play key roles in fertility and reproduction. They influence other aspects of health, too, including cognitive function, bone health, and risk of developing cardiovascular disease and cancer.

A molecule composed of carboxylic acid with a long hydrocarbon chain that is either saturated or unsaturated. Fatty acids are important components of cell membranes and are key sources of fuel because they yield large quantities of ATP when metabolized. Most cells can use either glucose or fatty acids for this purpose.

Flavonoid are widely distributed in plants, fulfilling many functions. Flavonoids have been shown to have a wide range of biological and pharmacological activities in animal, human, and in-vitro studies. Examples include anti-allergic, anti-inflammatory, antioxidant, antimicrobial, anti-cancer, and anti-diarrheal activities.

A type of water-soluble B-vitamin, also called vitamin B9. Folate is critical in the metabolism of nucleic acid precursors and several amino acids, as well as in methylation reactions. Severe deficiency in folate can cause megaloblastic anemia, which causes fatigue, weakness, and shortness of breath. Certain genetic variations in folate metabolism, particularly those found in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene influences folate status. Inadequate folate status during early pregnancy increases the risk of certain birth defects called neural tube defects, or NTDs, such as spina bifida, anencephaly, and other similar conditions. Folate deficiency and elevated concentrations of homocysteine in the blood are associated with increased risk of cardiovascular disease. Low folate status and/or high homocysteine concentrations are associated with cognitive dysfunction in aging (from mild impairments to dementia). The synthetic form of folate is called folic acid. Sources of folate include most fruits and vegetables, especially green leafy vegetables.

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.

The ability of a particular substance, such as an antigen or epitope, to provoke an immune response in the body of a human or animal.

A critical element of the body’s immune response. Inflammation occurs when the body is exposed to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective response that involves immune cells, cell-signaling proteins, and pro-inflammatory factors. Acute inflammation occurs after minor injuries or infections and is characterized by local redness, swelling, or fever. Chronic inflammation occurs on the cellular level in response to toxins or other stressors and is often “invisible.” It plays a key role in the development of many chronic diseases, including cancer, cardiovascular disease, and diabetes.

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 cytokine that plays roles in immune function. IL-4 regulates antibody production, hematopoiesis, and inflammation, and drives T-cell responses. It can exert both pro- and anti-inflammatory properties, depending on the physiological context. IL-4 also plays roles in learning and memory.

Experiments that are performed using cells or microorganisms outside of their normal biological context and are often done in a test tube or petri dish.

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 class of proteins present in many edible plants, such as grains or legumes. Lectins are carbohydrate-binding molecules. They have been referred to as antinutrients for their ability to impair absorption of some nutrients. Many lectins possess hemagglutinin properties, which means they can bind to blood cells and cause them to aggregate. Cooking typically denatures lectins in foods.

A type of white blood cell. Leukocytes are involved in protecting the body against foreign substances, microbes, and infectious diseases. They are produced or stored in various locations throughout the body, including the thymus, spleen, lymph nodes, and bone marrow, and comprise approximately 1 percent of the total blood volume in a healthy adult. Leukocytes are distinguished from other blood cells by the fact that they retain their nuclei. A cycle of prolonged fasting has been shown in animal research to reduce the number of white blood cells by nearly one-third, a phenomenon that is then fully reversed after refeeding.^[1]

The three basic components of the human diet. Macronutrients are consumed in large quantities and provide necessary energy for the body. They include carbohydrates, fats, and proteins.

A type of white blood cell. Macrophages engulf and digest cellular debris, foreign substances, microbes, cancer cells, and oxidized LDL in a process called phagocytosis. After phagocytizing oxidized LDL, macrophages are referred to as foam cells.

The collection of genomes of the microorganisms in a given niche. The human microbiome plays key roles in development, immunity, and nutrition. Microbiome dysfunction is associated with the pathology of several conditions, including obesity, depression, and autoimmune disorders such as type 1 diabetes, rheumatoid arthritis, muscular dystrophy, multiple sclerosis, and fibromyalgia.

A collective term for the community of commensal, symbiotic, and pathogenic microorganisms that live in a particular environment. The human body has multiple microbiotas, including those of the gut, skin, and urogenital regions.

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.

A type of white blood cell, also known as a granulocyte. Neutrophils are the most abundant form of blood cell, comprising approximately 60 percent of total cells. They ingest, kill, and digest microbial pathogens, and are the first cells recruited to acute sites of injury. Neutrophils can infiltrate brain structures, driving inflammation and increasing the risk for neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease.

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.

A type of polyunsaturated fat that is essential for human health. Omega-3 fatty acids influence cell membrane integrity and affect the function of membrane-bound cellular receptors. They participate in pathways involved in the biosynthesis of hormones that regulate blood clotting, contraction and relaxation of artery walls, and inflammation. They have been shown to help prevent heart disease and stroke, may help control lupus, eczema, and rheumatoid arthritis, and may play protective roles in cancer and other conditions. Omega-3 fatty acids include alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). ALA is found mainly in plant oils such as flaxseed, soybean, and canola oils. DHA and EPA are found in fish and other seafood. The human body can convert some ALA into EPA and then to DHA, but the efficiency of the process varies between individuals.

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 cell, such as a white blood cell, that engulfs and absorbs waste material, harmful microorganisms, or other foreign bodies in the bloodstream and tissues.

Any enzyme that breaks down a protein into smaller subunits. Proteases can be found in Animalia, Plantae, Fungi, Bacteria, Archaea, or viruses.

A study in which people are randomly allocated to receive one of several clinical interventions. One of these interventions is the standard of comparison or control. The control may be a standard practice, a placebo, or no intervention at all.

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.

The daily nutrient goals for essentially all healthy people. RDAs are calculated by determining the Estimated Average Requirements (the average amount of nutrients that half of all healthy people in any given demographic need each day) and adding two standard deviations. This ensures that the RDAs exceed the requirements of approximately 97.5% of the population.

Also known as T regulatory cells or Tregs. A component of the immune system that suppress immune responses of other cells. This is an important "self-check" build into the immune system to prevent excessive reactions. Regulatory T cells come in many forms with the most well-understood being those that express CD4, CD25, and Foxp3 (CD4+CD25+ regulatory T cells).

An enzyme that facilitates the generation of complementary DNA. In viruses, reverse transcriptases convert viral RNA into a complementary DNA, which can then be integrated into the host’s genome. In humans, the reverse transcriptase telomerase maintains and extends the length of telomeres.

Fatty acids that contain fewer than six carbons in their chemical structure. SCFAs are produced by the gut microbiota during the fermentation of dietary fiber. They provide energy to colonic cells and are crucial to gut health. In addition, SCFAs may play roles in the prevention and treatment of metabolic syndrome, inflammatory bowel disorders, and certain types of cancer. Some evidence suggests SCFAs can cross the blood-brain barrier to affect brain function. The principal SCFAs produced in the human gut are acetate, propionate, and butyrate.

A molecule that allows cells to perceive and correctly respond to their microenvironment, which enables normal cellular function, tissue repair, immunity, cognition, and more. Hormones and neurotransmitters are examples of signaling molecules. There are many types of signaling molecules, however, including cAMP, nitric oxide, estrogen, norepinephrine, and even reactive oxygen species (ROS).

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.

The primary male sex hormone. Testosterone is critical to the maintenance of fertility and secondary sexual characteristics in males. Low testosterone levels may increase risk of developing Alzheimer’s disease.

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 fat-soluble vitamin. Vitamin A is a collective term that includes retinol, retinal, and retinyl esters. Vitamin A plays key roles in immune function, reproduction, and cellular communication. It is best known for its role in supporting eye health and the processes involved in vision. Vitamin A also supports cell growth and differentiation and participates in the normal formation and maintenance of the heart, lungs, kidneys, and other organs. Dietary sources of vitamin A include liver, fish oils, milk, eggs, leafy green vegetables, orange and yellow vegetables, tomato products, fruits, and some vegetable oils.

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.