The Hormesis solution

Enhancing sirtuin activity with sirtuin-activating compounds

These sirtuin pathways exist in plants as well and they get turned on in response to stress. And we call this hormesis, the idea that when we eat stressed plants, we get those molecules and they help our bodies.” - Dr. David Sinclair Energy stress isn't the only activator of sirtuins. Some naturally occurring and synthetic compounds, called sirtuin-activating compounds, or STACs, may provide a way to tap into the benefits of this biology as well. For example, resveratrol, a naturally occurring compound found in red grapes and other plants, is a potent STAC. It protects the plants in which it is found from environmental stressors and disease. When ingested by humans, resveratrol binds to sirtuins, altering their affinity for NAD+ and their protein substrates, thereby increasing sirtuins' activity. As such, resveratrol presents a promising therapeutic strategy to ameliorate age-related diseases and extend healthspan. Hormesis uses a patented form of resveratrol. Through a process of fermentation, the compound becomes 50 times more effective at enhancing sirtuin activity, when applied to the skin. Fisetin, a compound found in fruits and vegetables such as strawberry, apple, persimmon, grape, onion, and cucumber. Like other polyphenols such as resveratrol, is a sirtuin-activating compound and has been shown in laboratory studies to extend the life of simple organisms like yeast, worms, and flies. Fisetin has been shown to be an effective senolytic agent, with effects of increased lifespan, minimized senescence markers in tissues, and reduced age-related pathologies.

Manipulation of cellular levels of NAD+ as a strategy for slowing skin aging

We’ve shown that NMN and others have shown for NR that it also helps with blood flow and actually mimics exercise and regrows the vascular system.” - Dr. David Sinclair As we age, however, the NAD+ levels in our bodies decline, reducing STAC’s potency. A few candidates have emerged as a means to manipulate or "boost" NAD+ levels in the body. The most well-studied NAD+ boosters are nicotinamide riboside nicotinamide mononucleotide, and myristyl nicotinate which have been shown to ameliorate age-associated diseases in studies. Hormesis uses the NAD+ boosters to help maintain cellular levels of NAD+, thereby facilitating NAD+-dependent cellular activities, such as mitochondrial metabolism, regulation of sirtuins, and PARP activity.

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