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Plants produce a variety of chemicals in response to external stressors, such as drought or fungal attack. When humans ingest these compounds, our cells "read" their chemical signals and switch on cellular mechanisms that protect us not only from the plant compound but also the environmental stressors to which we are exposed on a daily basis, such as air pollution or overexposure to UV radiation. This capacity of plant-based compounds to activate human cellular stress response pathways that confer protective effects is due to a biological phenomenon known as xenohormesis. In this clip, Dr. David Sinclair describes how plant-based compounds activate cellular protective mechanisms in humans.
David: I suppose people are interested in the plant world and what we eat, these same pathways, these sirtuin pathways exist in plants as well and they get turned on in response to stress. And we call this xenohormesis, the idea that when we eat stressed plants, we get those molecules and they help our bodies. So resveratrol, going back to that old chestnut, it's a great molecule that is produced when the grapes get stressed and...
Rhonda: It's got fungus, right?
David: Well, fungus will stimulate it.
Rhonda: Fungus stimulate it, okay.
David: Yeah. Or lack of water. So when they harvest red wine, they hope for a dry season, that'll boost the resveratrol levels and other good polyphenol molecules. And we think that...I think that when you ingest those molecules, the sirtuins have evolved to sense the plant world and if your food is stressed out, your body will hunker down and become fitter as a result of sensing that because, you know, we can see crops that are dying or if the water table's drying up, maybe we can sense that, but little animals that we evolved from or even, you know, a squirrel, it's too dumb to know that its food supply's stressed out, its body has to take care of that message.
Rhonda: Yes. So the resveratrol is activating all these stress response pathways that are basically, you know, in our, you know, we have in our body and basically turning on all these genes that are helping you deal with stress. But they're, like, staying activated for longer. And so, when, you know, basically aging, which is a stress, you're basically dealing with aging better in a way. Right?
David: Couldn't put it myself. And then the opposite, if you spend your whole day sitting, or typing, or you're always satisfying your hunger, your sirtuins, and your other pathways, AMP kinase, mTOR, they say, "Hey, times are good. Let's just grow tissue, go forth, multiply and not build a sustainable body in the long run." Because there's always a tradeoff, which Tom Kirkwood called the disposable soma hypothesis. And it seemed to be very true. So you want to always have your body in a state of a little bit of stress, hormesis, we call that.
Rhonda: Yes. People that are listening to the podcast have heard me talk about hormesis quite a bit. My favorite is sulforaphane, the molecule in the cruciferous vegetables.
An enzyme that plays multiple roles in cellular energy homeostasis. AMP kinase activation stimulates hepatic fatty acid oxidation, ketogenesis, skeletal muscle fatty acid oxidation, and glucose uptake; inhibits cholesterol synthesis, lipogenesis, triglyceride synthesis, adipocyte lipolysis, and lipogenesis; and modulates insulin secretion by pancreatic beta-cells.
A class of edible plants from the Brassicaceae, Capparaceae, and Caricaceae families, so named for their cross-shaped flowers. Crucifers contain glucosinolates and myrosinase, which react to form isothiocyanates, a class of compounds with known beneficial health effects in humans. Cruciferous vegetables include arugula, broccoli, bok choy, Brussels sprouts, cabbage, capers, cauliflower, cress, collards, kale, kohlrabi, moringa, mustard, papaya, radish, rutabaga, turnips, wasabi, and watercress.
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.
An enzyme that participates in genetic pathways that sense amino acid concentrations and regulate cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription. mTOR integrates other pathways including insulin, growth factors (such as IGF-1), and amino acids. It plays key roles in mammalian metabolism and physiology, with important roles in the function of tissues including liver, muscle, white and brown adipose tissue, and the brain. It is dysregulated in many human diseases, such as diabetes, obesity, depression, and certain cancers. mTOR has two subunits, mTORC1 and mTORC2. Also referred to as “mammalian” target of rapamycin.
Rapamycin, the drug for which this pathway is named (and the anti-aging properties of which are the subject of many studies), was discovered in the 1970s and is used as an immunosuppressant in organ donor recipients.
A class of chemical compounds produced in plants in response to stressors. Polyphenols contribute to the bitterness, astringency, color, flavor, and fragrance of many fruits and vegetables. They often serve as deterrents to insect or herbivore consumption. When consumed in the human diet, polyphenols exert many health benefits and may offer protection against development of cancers, cardiovascular diseases, diabetes, osteoporosis, and neurodegenerative diseases. Dietary sources of polyphenols include grapes, apples, pears, cherries, and berries, which provide as much as 200 to 300 mg polyphenols per 100 grams fresh weight.
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.
An isothiocyanate compound derived from cruciferous vegetables such as broccoli, cauliflower, and mustard. Sulforaphane is produced when the plant is damaged when attacked by insects or eaten by humans. It activates cytoprotective mechanisms within cells in a hormetic-type response. Sulforaphane has demonstrated beneficial effects against several chronic health conditions, including autism, cancer, cardiovascular disease, diabetes, and others.
An adaptive physiological response in which bioactive compounds, produced by environmentally stressed plants, induce beneficial stress response pathways in animals, including humans. Xenohormetic responses ultimately confer stress resistance and longevity and may explain some of the beneficial effects of plant-based foods. The term xenohormesis stems from two terms: xeno (stranger) and hormesis (a protective physiological response induced by mild stressors). Polyphenols, isothiocyanates, and other plant compounds are thought to exhibit some of their beneficial properties by inducing a type of xenohormesis.
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