Longevity Articles

Sirtuins: A Guide to Understanding Your Longevity Genes

Sirtuins: A Guide to Understanding Your Longevity Genes

What are Sirtuins?

Sirtuins are commonly referred to as longevity genes. Recent research has focused on the potential benefits of activating sirtuins as a means of promoting health and extending lifespan. 

Sirtuins are a class of enzymes in the body that play important roles in cellular processes such as DNA repair, cell survival and metabolism. Sirtuins have also been implicated in the aging process. Studies have suggested that sirtuins play a key role in regulating cellular senescence, a process by which cells stop dividing and contribute to aging and age-related health decline. 

Why You Need a Sirtuin Supplement as You Age

Individuals who are interested in protecting their brain and heart health as they age would likely benefit from supplementing with sirtuin-activating supplements.

Additionally, due to the connection between sirtuin activation and longevity, those looking to bolster their longevity protocol should also consider including sirtuin-activating supplements. 

Sirtuins' Role in Longevity and Aging 

Sirtuins play a critical role in regulating cellular aging by repairing damaged DNA. When DNA becomes damaged, inflammation increases which accelerates the aging of cells. This process is often referred to as “inflammaging”. 

Studies have shown that activating sirtuins can extend lifespan in animals and reduce many of the hallmark signs of inflammaging. Activating sirtuins has been shown to increase longevity by delaying cellular senescence, repairing damaged DNA, reducing oxidative stress and promoting heart health.

Benefits of Sirtuin Activation

Sirtuin activation is linked to longevity in several animal models. While there are several ways sirtuins regulate cellular aging, some of the key longevity benefits of sirtuins include:

Supporting Cellular Health with Age

Senescent cells (also known as “zombie cells”; aged cells that stop dividing and are resistant to death) accumulate with age and have been linked to decreased longevity. Research shows that activating sirtuins can extend the lifespan of cells by 50%, delaying how long it takes for the cell to become senescent. 

Repairing Damaged DNA

DNA damage has been shown to contribute to the age-related health decline of the heart and brain. Activating sirtuins helps promote DNA repair and reduce the accelerated aging of cells. 

Reducing Oxidative Stress

Oxidative stress contributes to inflammaging, DNA damage and decreased longevity. Activating sirtuins has been shown to reduce oxidative stress. 

Improving Heart Health

With aging comes an increased susceptibility to a decline in heart health. Some sirtuins play a role in improving blood flow and reducing inflammation in blood vessels. Preventing an accelerated reduction of sirtuin activity may be effective to promote heart health with age. 

Sirtuin-Activating Supplements

A variety of supplements have been shown to activate sirtuins and promote longevity including resveratrol, pterostilbene and fisetin. Additionally, each of these supplements have been shown to promote longevity by improving brain health, reducing accumulation of senescent cells and decreasing oxidative stress. 


Resveratrol, an antioxidant-like molecule found in red grapes and wine, has been shown to activate sirtuins. Research shows resveratrol may protect the brain from symptoms of brain aging improving memory and delaying cognitive decline. 


Pterostilbene is a compound commonly found in fruits such as blueberries, cranberries and grapes. Supplemental form of pterostilbene has gained popularity due to its high antioxidant profile that has been found to support longevity. 

Research shows that pterostilbene is a potent sirtuin activator that promotes longevity by reducing oxidative stress and promoting brain health. 

resveratrol and pterostilbene


Fisetin is an antioxidant compound found in fruits such as strawberries and apples. Research shows that fisetin is one of the most effective sirtuin-activating supplements. Fisetin is a type of senolytic, a natural compound that has been shown to “kill off” zombie cells. Reducing the amount of zombie cells in the body may help reduce the risk of experiencing age-related issues, thus contributing to longevity.

Pro-Tip: NAD+ (a coenzyme needed by every cell in our bodies) serves as fuel for sirtuins. Maintaining healthy NAD+ levels may reduce the decline in sirtuin function that accompanies aging. One way to increase NAD+ levels is through supplemental NMN.

Experts recommend that individuals taking sirtuin-activating supplements consider taking an NAD+ boosting supplement, like NMN. Supplementing with a sirtuin-activating supplement along with a NAD +-boosting supplement is a powerful punch to any longevity protocol. 

ProHealth’s NMN Pro Complete combines NMN with Resveratrol (to boost NAD+ and activate sirtuins) and TMG (to support NMN) to make the perfect foundational longevity supplement blend. 

Main Takeaway

The relationship between sirtuins and longevity is complex and still not fully understood. There's a lot of ongoing research in this field, as well as the mechanisms by which sirtuins might influence longevity and the optimal strategies for activating sirtuins in different contexts. While more research needs to be done to determine best practices when taking sirtuin-activating supplements, resveratrol, pterostilbene and fisetin are all sirtuin-activating supplements that have been shown to promote longevity and should be considered a key piece in any longevity protocol. 

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