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.

A type of protein that acts on neurons in the central and peripheral nervous systems. BDNF is a type of neurotrophin – or growth factor – that controls and promotes the growth of new neurons. It is active in the hippocampus, cortex, cerebellum, and basal forebrain – areas involved in learning, long term memory, and executive function. Rodent studies suggest that lactate, one of many so-called exerkines, mediates some of the benefits of exercise on learning and memory via inducing neuronal BDNF expression.^[1] Exercise in combination with heat stress increases BDNF more effectively than exercise alone.^[2] BDNF is a profoundly universal point of convergence for mechanistically explaining essentially all known activities that promote brain health.

A substance whose presence is essential for the activity of an enzyme. Many minerals and vitamins are cofactors for enzymes.

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.

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

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.

A protein that provides the instructions for genes responsible for the regulation of cellular replication, resistance to oxidative stress, metabolism, and DNA repair. FOXO3 may play an integral part in both longevity and tumor suppression. Variants of FOXO3 are associated with longevity in humans. Humans with a more active version of this gene have a 2.7-fold increased chance of living to be a centenarian.

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 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]

The chief protein components of chromatin found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes acting as spools around which DNA winds, and playing a role in gene regulation.

A broad term that describes periods of voluntary abstention from food and (non-water) drinks, lasting several hours to days. Depending on the length of the fasting period and a variety of other factors, intermittent fasting may promote certain beneficial metabolic processes, such as the increased production of ketones due to the use of stored fat as an energy source. The phrase “intermittent fasting” may refer to any of the following:

• Time-restricted eating
• Alternate-day fasting
• Periodic fasting (multi-day)

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 hormone that regulates the sleep-wake cycle in mammals. Melatonin is produced in the pineal gland of the brain and is involved in the expression of more than 500 genes. The greatest influence on melatonin secretion is light: Generally, melatonin levels are low during the day and high during the night. Interestingly, melatonin levels are elevated in blind people, potentially contributing to their decreased cancer risk.^[1]

A gene coding for an enzyme that converts homocysteine into methionine; a critical step in the methyl cycle. Natural variation in this gene is common among healthy people, however, some variants have been reported to influence susceptibility to occlusive vascular disease, neural tube defects, Alzheimer’s disease and other forms of dementia, colon cancer, and acute leukemia.

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.

Nicotinamide adenine dinucleotide (NAD) is a coenzyme found in all living cells used to transfer chemical energy from a food source to the electron transport chain. It exists in two forms, an oxidized and reduced form abbreviated as NAD+ and NADH respectively. NAD levels rise during a fasting state and activates the SIRT1 pathway. NADH levels rise during the fed state and serve as reducing equivalents to produce ATP.

Nicotinamide adenine dinucleotide (NAD) is a coenzyme found in all living cells used to transfer chemical energy from a food source to the electron transport chain. It exists in two forms, an oxidized and reduced form abbreviated as NAD+ and NADH respectively. NAD levels rise during a fasting state and activates the SIRT1 pathway. NADH levels rise during the fed state and serve as reducing equivalents to produce ATP.

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.

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.

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 member of the sirtuin protein family. SIRT1 is an enzyme that deacetylates proteins that contribute to cellular regulation (reaction to stressors, longevity). It is activated by the phytochemical resveratrol as well as fasting.

Distinctive structures comprised of short, repetitive sequences of DNA located on the ends of chromosomes. Telomeres form a protective “cap” – a sort of disposable buffer that gradually shortens with age – that prevents chromosomes from losing genes or sticking to other chromosomes during cell division. When the telomeres on a cell’s chromosomes get too short, the chromosome reaches a “critical length,” and the cell stops dividing (senescence) or dies (apoptosis). Telomeres are replenished by the enzyme telomerase, a reverse transcriptase.