What Are Sirtuins And What Do They Do?

What are sirtuins? At their core, they are specialized enzymes that act as the guardians of your cells. They rely on NAD+, a molecule often compared to a cellular battery, to switch genes on or off, repair DNA, and regulate metabolism.

Scientists sometimes call them “longevity proteins”. That’s because in many animal models, they help extend lifespan and improve resilience to stress.

If you want to learn more about these interesting cellular defenders, we got you covered! In this article we will - as the title says - take a look at what are sirtuins, and what exactly do they do!

What Are Sirtuins In Humans?

Sirtuins are NAD+-dependent enzymes known as deacetylases or deacylases. This means they remove chemical “tags” from proteins and DNA-packaging histones, which changes how genes are expressed.

They work like editors who remove sticky notes from a manuscript. This allows the book of life (your DNA) to be read more clearly.

Humans have seven sirtuins (SIRT1 through SIRT7):

SIRT1, SIRT6, SIRT7: Found mainly in the nucleus, where they protect DNA and regulate gene expression.
SIRT2: Active in the cytoplasm, controlling the cell cycle.
SIRT3, SIRT4, SIRT5: Located in the mitochondria—the “power plants” of cells—where they tune energy production and oxidative stress.

Because each sirtuin works in a different part of the cell, together they form a coordinated defense system against aging and disease.

How Do Sirtuins Work In The Body?

Sirtuins sense cellular energy levels through NAD+ and adjust processes to keep cells alive and healthy.

Here are some functions that sirtuins perform:

DNA repair: Sirtuins recruit DNA repair enzymes to damaged sites, patching genetic errors like a team of construction workers fixing potholes before they spread.
Stress defense: They boost antioxidant systems, disarming reactive oxygen species (ROS)—harmful byproducts of metabolism that act like cellular rust.

Sirtuins And NAD+ What’s The Catch?

Sirtuins are NAD+-dependent. That means they only work when NAD+ is available. NAD+ levels rise during fasting, calorie restriction, or exercise, and fall as we age.

Imagine NAD+ as the electricity powering your house—when the current is strong, all appliances (sirtuins) can work. When it dims, they struggle.

What Do The 7 Sirtuins Do?

Each member of the family has a unique role:

SIRT1: Regulates cell’s response to (oxidative) stress.
SIRT2: Involved in regulating inflammation in the brain.
SIRT3: Works on regulating metabolism and anti-inflammatory responses.
SIRT4: Important for oxidative stress and glucose metabolism.
SIRT5: Influences metabolism and production of proteins.
SIRT6: Primarily works as an anti-inflammatory protein.
SIRT7: Regulates programmed cell death - apoptosis.

What Are Sirtuins And What Are Their Effects On Lifespan?

In yeast, increasing sirtuin activity extends lifespan —sometimes by as much as 70%. And mammals show similar effects. These effects are linked to improved DNA stability.

In mammals, the picture is more nuanced. While sirtuins clearly protect against age-related damage, direct lifespan extension in humans is not proven. However, they consistently linked to healthspan—the years lived in good health.

In other words, sirtuins may not guarantee you live longer, but they can help ensure you live better.

How Do Sirtuins Influence Oxidative Stress?

Many different sirtuins in humans are involved in regulating oxidative stress. They usually do so by controlling inflammatory pathways and DNA damage response proteins.

Oxidative stress occurs when reactive oxygen species (ROS) overwhelm the cell’s defenses, much like rust forming faster than you can clean it. ROS are produced during normal metabolism, especially in the mitochondria.

Sirtuins step in as rust-proofing agents. For instance, SIRT1 activates transcription factors like FOXO that increase antioxidant enzymes such as superoxide dismutase.

What Stimulates Sirtuins?

Calorie restriction, fasting, and exercise are natural triggers. When energy is scarce, NAD+ levels rise, and sirtuins switch on. This is why fasting often produces cellular benefits similar to anti-aging interventions.

Certain compounds also act as sirtuin activators:

Resveratrol (found in red grapes and berries) has been shown to activate SIRT1 pathways.
Curcumin (from turmeric) has been studied for its regulatory effects on sirtuins.

These foods don’t contain sirtuins themselves, but they send signals that encourage sirtuin pathways. It’s like ringing the factory bell to get workers moving.

How Do Sirtuins Connect to NAD+ And NMN?

Sirtuins cannot function without NAD+. As NAD+ declines with age, dropping by as much as 50%, sirtuin activity falters. This decline contributes to weaker DNA repair, less efficient metabolism, and greater vulnerability to oxidative stress.

NMN (nicotinamide mononucleotide) is a direct precursor to NAD+. Supplementing with NMN helps restore NAD+ levels, giving sirtuins the “battery charge” they need to keep running. It is like plugging your maintenance crew’s tools back into a full power source.

Final Thoughts: What Are Sirtuins

What are sirtuins? They are NAD+-dependent enzymes that act as the guardians of your cells. By repairing DNA, combating oxidative stress, and managing energy, they directly influence how gracefully you age.

While human studies are still ongoing, decades of research in animals and cells show that sirtuins are critical to extending healthspan.

You can support them naturally through lifestyle—fasting, exercise, plant-rich diets—and scientifically through NAD+ precursors like NMN.

Take control of your cellular health today with HealthspanX Ultra Pure NMN™.

References

Merksamer, P. I., Liu, Y., He, W., Hirschey, M. D., Chen, D., & Verdin, E. (2013). The sirtuins, oxidative stress and aging: an emerging link. Aging, 5(3), 144–150. https://doi.org/10.18632/aging.100544
Grabowska, W., Sikora, E., & Bielak-Zmijewska, A. (2017). Sirtuins, a promising target in slowing down the ageing process. Biogerontology, 18(4), 447–476. https://doi.org/10.1007/s10522-017-9685-9
Wu, Q. J., Zhang, T. N., Chen, H. H., Yu, X. F., Lv, J. L., Liu, Y. Y., Liu, Y. S., Zheng, G., Zhao, J. Q., Wei, Y. F., Guo, J. Y., Liu, F. H., Chang, Q., Zhang, Y. X., Liu, C. G., & Zhao, Y. H. (2022). The sirtuin family in health and disease. Signal transduction and targeted therapy, 7(1), 402. https://doi.org/10.1038/s41392-022-01257-8
McReynolds, M. R., Chellappa, K., & Baur, J. A. (2020). Age-related NAD+ decline. Experimental gerontology, 134, 110888. https://doi.org/10.1016/j.exger.2020.110888