An energy-carrying molecule present in all cells. ATP fuels cellular processes, including biosynthetic reactions, motility, and cell division by transferring one or more of its phosphate groups to another molecule (a process called phosphorylation).

A catecholamine hormone produced by the adrenal glands and some neurons. Adrenaline, also known as epinephrine, exerts many effects in the body, the most notable being those associated with the “fight or flight” response to stressors. The effects of epinephrine and norepinephrine (a related catecholamine) are mediated by adrenergic receptors, which act as the interface between the sympathetic nervous system and the cardiovascular system.

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.

The physiological process through which new blood vessels form from preexisting vessels. This is a normal and vital process in growth and development, wound healing, and in the formation of granulation tissue. However, it is also a fundamental step in the transition of tumors from a benign state to a malignant one.

One of two types of fat, or adipose, tissue (the other being white adipose tissue, or white fat) found in mammals. The primary function of brown adipose tissue is to generate body heat. In contrast to white adipocytes (fat cells), which contain a single lipid droplet, brown adipocytes contain numerous smaller droplets and a much higher number of mitochondria, which make it brown. Brown fat also contains more capillaries than white fat, since it has a greater need for oxygen than most tissues.

Emotional pressure suffered for a prolonged period over which an individual perceives he or she has no control. It involves an endocrine system response in which occurs a release of corticosteroids.

The body’s 24-hour cycles of biological, hormonal, and behavioral patterns. Circadian rhythms modulate a wide array of physiological processes, including the body’s production of hormones that regulate sleep, hunger, metabolism, and others, ultimately influencing body weight, performance, and susceptibility to disease. As much as 80 percent of gene expression in mammals is under circadian control, including genes in the brain, liver, and muscle.^[1] Consequently, circadian rhythmicity may have profound implications for human healthspan.

Proteins that preserve cell viability at low temperatures by binding to nucleic acids and, subsequently, controlling gene expression. Cold shock proteins have what is known as a "cold-shock domain," a sequence of amino acids whose expression is associated with cold and is thought to help cells survive in lower than optimal temperatures.

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.

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 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.

A technique that enables scientists to measure the expression levels of thousands of genes simultaneously in order to study the effects of certain treatments, diseases, and developmental stages on gene expression. Also used for genotyping and sometimes referred to as a "DNA chip" or a "biochip."

System of glands regulating the body through the production of hormones. The endocrine system's effects are slow to initiate, and prolonged in their response, lasting from a few hours up to weeks. In contrast, the nervous system sends information very quickly, and responses are generally short lived.

The single layer of cells that lines the interior of the blood and lymphatic vessels. The endothelium participates in blood flow, platelet aggregation, and vascular tone. It also regulates inflammation, immune function, and angiogenesis. Endothelial dysfunction is a systemic pathological condition broadly defined as an imbalance between vasodilating and vasoconstricting substances produced by (or acting on) the endothelium. It is a robust predictor of heart attack and stroke risk.

Beneficial stress that can be psychological, physical (e.g. exercise), or biochemical (hormesis) in nature.

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.

The process in which information stored in DNA is converted into instructions for making proteins or other molecules. Gene expression is highly regulated. It allows a cell to respond to factors in its environment and involves two processes: transcription and translation. Gene expression can be turned on or off, or it can simply be increased or decreased.

A naturally occurring substance capable of stimulating cellular growth, proliferation, healing, and differentiation. Growth factors typically act as signaling molecules between cells. Examples include cytokines and hormones that bind to specific receptors on the surface of their target cells.

A family of proteins produced by cells in response to exposure to stressful conditions. Heat shock proteins are expressed in response to heat as well as exposure to cold and UV light, and during wound healing and tissue remodeling. Many heat shock proteins function as chaperones by stabilizing new proteins to ensure correct folding or by helping to refold proteins that were damaged by cell stress. A 30-minute 73ºC sauna session in healthy young adults has been shown to cause a robust and sustained increase in the production of heat shock proteins for up to 48 hours afterward.^[1]

A sustained period of winter dormancy in warm-blooded animals. Hibernation is characterized by prolonged periods of inactivity and low nutrient intake.

Hypothermia is a medical emergency that occurs when your body loses heat faster than it can produce heat, causing a dangerously low body temperature. Normal body temperature is around 98.6 F (37 C). Hypothermia occurs as your body temperature passes below 95 F (35 C)

A component of the innate immune system. The inflammasome is expressed in the myeloid cells and promotes the maturation of the pro-inflammatory cytokines IL-1B and IL-18. It is responsible for activation of inflammatory processes.

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 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 pro-inflammatory cytokine that plays an important role as a mediator of fever and the acute-phase response. IL-6 is rapidly induced in the context of infection, autoimmunity, or cancer and is produced by almost all stromal and immune cells. Many central homeostatic processes and immunological processes are influenced by IL-6, including the acute-phase response, glucose metabolism, hematopoiesis, regulation of the neuroendocrine system, hyperthermia, fatigue, and loss of appetite. IL-6 also plays a role as an anti-inflammatory cytokine through inhibition of TNF-alpha and IL-1 and activation of IL-1ra and IL-10.

Supports a variety of functions including epinephrine flow, emotion, behavior, motivation, long-term memory, and olfaction. Emotional life is largely housed in the limbic system, and it has a great del to do with the formation of memories.

Long-term meditation is a practice where an individual trains the mind or induces a mode of consciousness designed to promote relaxation, build internal energy or develop a desired mental state. It can range from 20 minutes to an indefinite amount of time. Long-term meditation is associated with increased gray matter density in the brain stem.

A set of cell surface molecules that helps the immune system recognize foreign substances. The MHC binds to peptide fragments derived from pathogens and displays them on the cell surface so they will be recognized by the appropriate T-cells.

A cluster of at least three of five of the following medical conditions: abdominal (central) obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides, and low high-density lipoprotein (HDL) levels. Some studies estimate the prevalence in the USA to be 34 percent of the adult population. Metabolic syndrome is associated with the risk of developing cardiovascular disease and diabetes.

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.

A rapid-acting transcription factor that responds to harmful cellular stimuli, such as reactive oxygen species, IL-1B, bacterial endotoxin (lipopolysaccharide or "LPS"), ionizing radiation, and oxidized LDL. Incorrect regulation of NF-kB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development. Several viruses, including the AIDS virus HIV, have binding sites for NF-kB. In the case of HIV, the presence of NF-kB is believed to be involved in switching the virus from a latent to an active state.

A substance produced in the brain. Norepinephrine acts as a hormone and neurotransmitter and is best known for its role in the body’s “fight or flight” response to stress. Its role as a neurotransmitter has been exploited as a molecular target for a class of drugs known as norepinephrine reuptake inhibitors, which were developed for the purpose of treating disorders ranging from ADHD to narcolepsy and depression. Norepinephrine also plays a role in converting white adipose tissue into brown adipose tissue via an uncoupling protein 1 (UCP-1) mediated mechanism.

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.

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 cold-shock protein that is induced by exposure to low temperatures, such as those that encountered during hibernation. In a cell model of Parkinson's disease, RBM3 provided neuroprotection, suggesting that RBM3 induction may be a suitable strategy for Parkinson's disease therapy.^[1]

Increased respiration elevates the blood pH beyond the normal range (7.35-7.45) with a concurrent reduction in arterial levels of carbon dioxide. This condition is one of the four basic categories of disruption of acid-base homeostasis.

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 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 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.

A metabolic disorder characterized by high blood sugar and insulin resistance. Type 2 diabetes is a progressive condition and is typically associated with overweight and low physical activity. Common symptoms include increased thirst, frequent urination, unexplained weight loss, increased hunger, fatigue, and impaired healing. Long-term complications from poorly controlled type 2 diabetes include heart disease, stroke, diabetic retinopathy (and subsequent blindness), kidney failure, and diminished peripheral blood flow which may lead to amputations.

A protein found in the mitochondria of brown adipose tissue, previously known as thermogenin. UCP1 is expressed only in brown adipose tissue, a specialized tissue which functions to produce heat via non-shivering thermogenesis.

Originally known as vascular permeability factor (VPF). VEGF's normal function is to create new blood vessels during embryonic development, after injury, in muscle following exercise, and new vessels (collateral circulation) to bypass blocked vessels. When VEGF is overexpressed, it can contribute to disease. Solid cancers cannot grow beyond a limited size without an adequate blood supply, and cancers that can express VEGF are able to grow and metastasize.