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 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].

The shrinking or wasting away of cells, organs, or tissues that may occur as part of a disease process, trauma, or aging.

An intracellular degradation system involved in the disassembly and recycling of unnecessary or dysfunctional cellular components. Autophagy participates in cell death, a process known as autophagic dell death. Prolonged fasting is a robust initiator of autophagy and may help protect against cancer and even aging by reducing the burden of abnormal cells.

The relationship between autophagy and cancer is complex, however. Autophagy may prevent the survival of pre-malignant cells, but can also be hijacked as a malignant adaptation by cancer, providing a useful means to scavenge resources needed for further growth.

A measurable substance in an organism that is indicative of some phenomenon such as disease, infection, or environmental exposure.

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.

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

Important for the endocrine enhancing properties of exercise. Exerkines are exercise-induced hormonal-like factors which mediate the systemic benefits of exercise through autocrine, paracrine, and/or endocrine properties.^[1]

A small organ located within the brain's medial temporal lobe. The hippocampus is associated primarily with memory (in particular, the consolidation of short-term memories to long-term memories), learning, and spatial navigation. Amyloid-beta plaque accumulation, tau tangle formation, and subsequent atrophy in the hippocampus are early indicators of Alzheimer’s disease.

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.

An essential mineral present in many foods. Iron participates in many physiological functions and is a critical component of hemoglobin. Iron deficiency can cause anemia, fatigue, shortness of breath, and heart arrhythmias.

A chemical that causes Parkinson's disease-like symptoms. MPTP undergoes enzymatic modification in the brain to form MPP+, a neurotoxic compound that interrupts the electron transport system of dopaminergic neurons. MPTP is chemically related to rotenone and paraquat, pesticides that can produce parkinsonian features in animals.

A precursor molecule for the biosynthesis of nicotinamide adenine dinucleotide (NAD+), a coenzyme that participates in the production of cellular energy and repair. NMN helps maintain cellular levels of NAD+, thereby facilitating NAD+-dependent cellular activities, such as mitochondrial metabolism, regulation of sirtuins, and PARP activity. Animal studies have demonstrated that NMN administration is effective in increasing NAD+ levels across multiple tissues while improving the outcome of a variety of age-related diseases. Although NMN administration has proven to be safe and to effectively increase NAD+ levels in rodents, the safety and efficacy of NMN supplementation in humans remain unknown. NMN is available in supplement form and is present in various types of food, including broccoli, avocado, and beef. It is also an intermediate compound in the NAD+ salvage pathway, the recycling of nicotinamide into NAD+.

A precursor molecule for the biosynthesis of nicotinamide adenine dinucleotide (NAD+), a coenzyme that participates in the production of cellular energy and repair. NMN helps maintain cellular levels of NAD+, thereby facilitating NAD+-dependent cellular activities, such as mitochondrial metabolism, regulation of sirtuins, and PARP activity. Animal studies have demonstrated that NMN administration is effective in increasing NAD+ levels across multiple tissues while improving the outcome of a variety of age-related diseases. Although NMN administration has proven to be safe and to effectively increase NAD+ levels in rodents, the safety and efficacy of NMN supplementation in humans remain unknown. NMN is available in supplement form and is present in various types of food, including broccoli, avocado, and beef. It is also an intermediate compound in the NAD+ salvage pathway, the recycling of nicotinamide into NAD+.

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 chemical reaction that removes an acetyl functional group from a chemical compound. The presence of the acetyl functional group plays an important role in the synthesis, stability and localization of about 85% of human proteins.^[1] During fasting, falling acetyl CoA levels in the cytosol initiate protein deacetylation and initiates autophagy. In general, protein deacetylation, whether from so-called caloric restriction mimetics or nutrient deprivation, is an important general inducer of autophagy.

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

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 class of enzymes that influence that influence aging and longevity through multiple molecular pathways. Sirtuins regulate a variety of metabolic processes, including release of insulin, mobilization of lipids, response to stress, and modulation of lifespan. They also influence circadian clocks and mitochondrial biogenesis. Sirtuins are activated when NAD+ levels rise. The dependence of sirtuins on NAD+ links their enzymatic activity directly to the energy status of the cell via the cellular NAD+:NADH ratio, the absolute levels of NAD+, NADH or nicotinamide or a combination of these variables. There are seven known sirtuins, designated as Sirt1 to Sirt7.

The highest level of intake of a given nutrient likely to pose no adverse health effects for nearly all healthy people. As intake increases above the upper intake level, the risk of adverse effects increases.

A progressive worsening of memory and other cognitive functions that is thought to be due to chronic reduced blood flow to the brain which is commonly due to the accumulation of cholesterol and other substances in the blood vessel walls that obstruct the flow of blood to the brain.