You may have encountered the term “sirtuins” recently, possibly due to the buzz surrounding the SIRTfood diet or the ongoing debate about the supplement resveratrol. Sirtuins are a group of enzymes that participate in various physiological functions within our bodies. Think of them as tiny superheroes operating within us, potentially impacting our lifespan.
Throughout this series, we will explore the world of sirtuins: what they are and their significance, how we can influence their activity through dietary choices (including the SIRTfood diet) and exercise, and lastly, we will examine the popular supplement resveratrol.
Keep reading to discover the captivating group of enzymes and their role within our bodies.
What are sirtuins?
Sirtuins are a group of seven enzymes in our bodies that have many important physiological functions and play a role in metabolism, antioxidant protection, and cell cycle regulation (1). They are passed down from low-level organisms, such as yeast, to humans. They are present in different parts of our cells (mitochondria, nucleus, cytoplasm) and organs. Various sirtuins (Sir1-Sir7) are involved in distinct processes, however in this text, we will use the general term “sirtuins”. And if you are curious where the “sirtuin” term comes from- SIR stands for Silent Information Regulator.
While the concept of the SIRTfood diet (derived from sirtuin) may be a recent buzz, the exploration of the enzymes dates back to the early 1970s (1). However, it wasn’t until 1991 that their prospect for longevity was realized. A few years later, by adding one kind of sirtuin to DNA, scientists could extend the replication life of yeast compared to control. Over the next years, the life cycle of worms was extended. In 2003, Prof. David Sinclair showed that the activity of sirtuins could be modified by other substances, such as resveratrol. Since then, much research has focused on understanding the cellular mechanisms of sirtuins and how we could harness them to improve longevity.
What are the main functions of sirtuins in the body, and why are they important?
They are important due to their potential impact on life extension.
It is known that when the gene responsible for the expression of sirtuins is deleted in yeast, their lifespan is reduced (2). Additionally, the activity of individual sirtuins in cells decreases with age, making them an excellent therapeutic target for longevity. Understanding why that happens could help researchers figure out how to design interventions for longevity.
Some of the most important functions of sirtuins are (1), (3):
- Prevent DNA damage
- Prevent the formation of cancer cells
- Play a crucial role in the antioxidant defense and inflammatory reactions
- Increase resistance to cellular stress
- Play a role in circadian rhythms
Sirtuins have many important functions, but how they are regulated on a cellular level is still debated.
How are sirtuins regulated in the cells?
As the human body is very sophisticated and there are several differences between it and other species, understanding how sirtuins work can be complex. On a high level, sirtuins are enzymes that act like catalysts in our body, speeding up important chemical reactions. They belong to a group of enzymes called deacetylases, which means they’re good at removing something called an “acetyl group” from other proteins.
Sirtuins are NAD+ (nicotinamide adenine dinucleotide) dependent enzymes. NAD+ is present in all living cellsand plays a huge role in various cellular activities, such as how we use energy and handle chemical reactions. As we discussed in our earlier article on NMN-the debated longevity drug, the NAD+ levels in the body decrease with aging. That decrease is associated with lower energy production in our cell’s energy centers (mitochondria), oxidative stress, DNA damage, cognitive problems, and inflammation. Sirtuins are NAD+ dependent enzymes, meaning they need NAD+ to do their job. When NAD+ levels are high, sirtuins are activated and can deacetylate target proteins. Such deacetylation processes are important for gene expression, DNA repair, metabolism, and stress response.
NAD+ levels have been implicated to longevity as it is known that as we age, the levels of NAD+ are decreasing and potentially affecting the activity of sirtuins. This led to strategies to boost the NAD+ levels and influence sirtuin activity. The most common interventions include exercise, diet, and supplements, which we will discuss in our next posts.
In conclusion, sirtuins stand as a vital tool in the arsenal that could potentially extend our years of good health. Although there is an ongoing debate on the effect of SIRT proteins on human longevity, and many questions remain, it is exciting to see what future research will reveal.
References
- Ziętara P, Dziewięcka M, Augustyniak M. Why Is Longevity Still a Scientific Mystery? Sirtuins—Past, Present and Future. Int J Mol Sci. 2022 Dec 31;24(1):728.
- Kaeberlein M, McVey M, Guarente L. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev. 1999 Oct 1;13(19):2570–80.
- Bonkowski MS, Sinclair DA. Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds. Nat Rev Mol Cell Biol. 2016 Nov;17(11):679–90.
