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.

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.

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.

A drug commonly used for the treatment of type 2 diabetes. Metformin is in a class of antihyperglycemic drugs called biguanides. It works by decreasing gluconeogenesis in the liver, reducing the amount of sugar absorbed in the gut, and increasing insulin sensitivity. A growing body of evidence indicates that metformin modulates the aging processes to improve healthspan and extend lifespan. Furthermore, metformin may prevent genomic instability by scavenging reactive oxygen species, increasing the activities of antioxidant enzymes, inhibiting macrophage recruitment and inflammatory responses, and stimulating DNA damage responses and DNA repair.[1]

[1] Najafi, Masoud, et al. "Metformin: Prevention of genomic instability and cancer: A review." Mutation Research/Genetic Toxicology and Environmental Mutagenesis 827 (2018): 1-8.

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 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 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 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.

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.