https://siimland.com/list-of-sirtuin-activating-compounds-stacs/
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DNA damage occurs throughout your lifetime. This decreases cells’ ability to divide and conduct other processes properly, thus suppressing growth and proliferation. When cells stop dividing they become senescent zombie cells and stop living longer.
Researchers have found that there are certain enzymes, metabolic pathways, and genes that regulate the process of aging. They usually activate in response to stress and low nutrient availability.
One of the few known ways of increasing lifespan in virtually all species is calorie restriction and eating less. Animals like rhesus monkeys and mice live longer when fed 20-40% fewer calories.
Calorie restriction doesn’t work in life-extension in the absence of autophagy and sirtuins. Deficient autophagy promotes aging and disease. Mice and yeast that are defective in autophagy don’t live longer despite consuming fewer calories whereas sufficient autophagy allows these effects to take place.
Sirtuins, which are NAD-dependent longevity genes that help to repair broken DNA and increase lifespan. Sirtuins detect cellular energy balance and modulate the circadian epigenome.
Sirtuins and NAD
You need NAD+ for sirtuins to work. NAD+ is a co-enzyme that regulates many biological processes and energy production. It plays a key role in regulating metabolism and circadian rhythms through sirtuins. Without NAD your cells would lack the resources to function properly, thus pre-dispose them to aging.
Disrupting circadian rhythms suppresses the NAD+ dependent SIRT1 gene which then lowers the availability of NAD+. NAD decreases with age and lower NAD levels may accelerate aging. It’ll definitely lower your energy potential.
SIRT1 is the main sirtuin gene that controls circadian rhythms and connects it with cellular metabolism. SIRT1 also delays aging and extends lifespan in mice. Enhanced SIRT1 activity can have widespread health benefits in humans as well.
Aging also decreases melatonin levels and weakens the expression of circadian gene expression, causing sleep fragmentation and age-related diseases. Mice with circadian gene knockouts show accelerated aging, shortened lifespan, cancer, and other ailments. Fortunately, it’s been found that calorie restriction can reverse the rewiring of disrupted circadian rhythms thanks to increased sirtuin and NAD, thus alleviating the side-effects of aging.
Sirtuin Activating Compounds STACs
One of the most effective and well-known ways of activating sirtuins and autophagy is to restrict calories and fast. This will signal the body that it’s in a survival scenario and needs to activate these longevity genes.
Sirtuin-activating compounds (STACs) are compounds that affect sirtuins and mimic calorie restriction. They have the potential to slow down aging and protect against age-related diseases like Alzheimer’s.
STACs were discovered by Konrad Howitz and David Sinclair who published a paper on how resveratrol – a plant polyphenol – activates SIRT1 and extends the lifespan of yeast. This ignited the longevity industry’s interest in these molecules that may be useful in extending human lifespan as well. Other examples of STACs include quercetin, pterostilbene, fisetin, butein, and many others.
STACs work in conjunction with other longevity pathways like AMPK, autophagy, mTOR inhibition, FOXO proteins, PGC-1 alpha, etc. They stimulate what David Sinclair calls the ’survival circuit’ – the epigenetic information that forces the body to adapt to environmental stress and energy deprivation.
List of Sirtuin Activating Compounds
- It’s thought that resveratrol can mimic caloric restriction by activating SIRT1. However, those claims have been disputed and they’re dependent on other background pathways. Nevertheless, resveratrol has been still found to mimic caloric restriction including many of its benefits such as reduced oxidative stress, lower inflammation, improved cardiovascular function, and enhanced cognition. Resveratrol can inhibit mTOR and activate AMPK which has similar benefits on longevity as sirtuins.
- Polyphenols found in bitter vegetables, olive oil, dark chocolate, curcumin, ginger, ginseng, and dark berries can modulate sirtuins. Coffee and teas also have polyphenols. Coffee, broccoli, and spices activate the Nrf2 pathway, which can cause the antioxidant defense effect.
- Curcumin activates SIRT1 and blocks the neurotoxicity of beta-amyloid plaques found in Alzheimer’s. Ginger, Cinnamon, and Turmeric are a part of my daily antioxidant consumption.
- Quercetin is the most widely consumed flavonoid in the human diet with many antioxidant benefits and it activates the SIRT1. It’s found in elderberries, red onions, hot peppers, cranberries, kale, and tomatoes. Catechins, quercetin, butein, fisetin, and kaempferol are also compounds found in those same foods to increase sirtuins.
- DHA increases SIRT1 and improves vascular function of the blood vessels and cerebral flow. Best DHA sources are fatty fish, eggs, and algae.
- Zinc is important in maintaining SIRT1 activity. Zinc is found in seafood, fish, and meat. However, these foods also increase mTOR signaling, which can counterbalance the effects of sirtuins.
- Nicotinamide Riboside (NR) is an NAD+ precursor that helps with energy metabolism. It’s also a form of vitamin B3 that’s found in raw dairy, yeast, mushrooms or niacin supplements. This may help to shuttle SIRT1.
Despite being a NAD precursor, NR inhibits the NAD+ consuming sirtuins. NR and niacin but not nicotinamide have been shown to increase hepatic levels of O-acetyl-ADP-ribose, which gets created when sirtuins consume NAD+.
How to Take STACs
Although sirtuins and autophagy can promote longevity, they’re not something you want to activate all the time. This would inhibit the body’s anabolic processes of maintaining and building muscle mass.
The best time to take sirtuin-activating compounds is either in a fasted state when you’re not that physically active or trying to treat a certain illness. Taking STACs and autophagy boosters around exercise can actually negate the beneficial adaptations that occur from the exercise by shutting down the oxidative stress signal. That’s why I take things like curcumin or polyphenols only on my rest days when I’m trying to help my body recover and go into less of an anabolic state.
To achieve the best of both worlds – anabolism and catabolism – you’d want to practice some form of intermittent fasting that would activate sirtuins and then eat a nutrient-dense diet. This facilitates muscle growth while still gives you the activation of sirtuins and autophagy.
Intermittent fasting can mimic the effects of calorie restriction without restricting your calories as much and it’s definitely a more potent stimulator of sirtuins. In a fasted state you activate autophagy, even more than with a low-cal diet, while still being able to feed yourself. The timing of when you eat and when you don’t give you unique metabolic effects unachievable with the regular way of eating.
