The Longevity Genes: Why Sirtuins are so important to cell health
For anyone who understands well that the biological aging process can be influenced in a way that improves our healthspan, you’ll appreciate the role of NAD in slowing the aging process. But it’s actually NAD’s activation of the longevity genes called sirtuins that gives us the results we are looking for. Understanding the different sirtuins and their role in slowing the aging process is, therefore, important when making interventions to your lifestyle.
Sirtuins are key to switching off genes
The discovery of sirtuins is one of the greatest breakthroughs in aging research. The sirtuin protein family contains seven members, each numbered 1-7 - SIRT1, SIRT 2, SIRT 3 and so on. Between them they have a wide range of functions in the body. They are found in various locations in the cell depending on that function. Sirtuins are mainly involved in maintaining balance within the cell and to do this they are dependent on NAD+.
The DNA in our cells provides the instructions for all the genes our cells need throughout our lifetime. It is estimated there are around 25,000 genes in our DNA, so our cells have developed various mechanisms to control which genes we express and when. When we are young and growing, we require different genes than when we are older.
Sirtuins - particularly those that live in the nucleus and closest to our DNA - are one of these regulatory mechanisms. Their job is to tell the cell which genes are not needed right now. They do this by removing markers (called ‘acetyl’ markers) from certain places of the DNA. This signals that this gene is not needed right now so the DNA folds up tightly making that gene inaccessible.
Essential to Lifespan
For nearly twenty years now, SIRT3 has been a protein of particular interest in the field of antiaging because of an association with very long lifespan. Located only in the mitochondria, SIRT3 is well known for its ability to eliminate reactive oxygen species and, as a result, to prevent the development of cancerous cells or cell death. Interestingly, SIRT3 is also being investigated for its neuroprotective properties as well.
As part of the mitochondria’s process in making the cell’s energy (ATP), highly reactive versions of oxygen are generated as byproducts. The problem with this is that, if they are not captured, they can be extremely damaging to the cell. SIRT3 helps to protect the cells from this damage by highly reactive oxygen species by activating antioxidant enzymes. This is why SIRT3 has been so clearly associated with antiaging and anti-cancer properties.
As we age and SIRT3 levels decline, these reactive oxygen species cause more and more cell damage and eventually communication between the mitochondria and the nucleus breaks down.
Controlling the Cell’s Energy Production
Sirtuins were initially discovered in yeast and since then there has been great interest in understanding their roles in humans. The human version of the gene discovered in yeast is SIRT1 and is the best studied of all sirtuins.
SIRT1 regulates several pathways that are involved in metabolism, the chemical processes that change food into energy. In the liver, SIRT1 promotes the creation of and prevents the breakdown of glucose.
To ensure that energy production is meeting the demands of the cell, it is very important for the nucleus of the cell to communicate with the mitochondria, the energy factory of the cell. To do this, there are sirtuins located specifically in the mitochondria to address a number of different issues. SIRT7 controls the creation of new mitochondria and helps during energy production. SIRT4 has the opposite effect on the mitochondria, decreasing ATP production.
Repairing DNA Damage
SIRT2 is found in the fluid part of the cell (the cytoplasm), which means it is able to travel between the nucleus and the mitochondria. It is mainly involved in the checkpoint that ensures there is no DNA damage within the cell before it enters cell division. If damage is detected, the cell can then decide whether to take time to repair the damage or breakdown the damaged cell completely. Maintaining the checkpoint is extremely important and is often disrupted in cancer.
SIRT6 has an essential role in the biological aging process and, specifically, addressing oxidative stress. This is because it is involved in DNA repair. When the DNA is damaged by oxidative stress, SIRT6 is part of the process of recruiting repair proteins. This means that, in older cells, when sirtuin levels decrease, the ability to repair oxidative stress is greatly reduced. This means DNA damage accumulates and this build-up of damage eventually contributes to age related diseases.
As we can see sirtuins are essential to almost every cellular process, and their functions will only increase as more research is conducted. Their link to aging is clear as so many of these processes decline with age. Therefore, maintaining sirtuin activation, through the NAD+ they rely on, is vital as we age.
Learn more about Sirtuin activation and NAD.
Learn more about the mitochondria: the key component to aging.
References;
Grabowska, W., Sikora, E. and Bielak-Zmijewska, A., (2017). Sirtuins, a promising target in slowing down the ageing process. Biogerontology, 18(4), pp.447-476.
Imai, S.I. and Guarente, L., (2014). NAD+ and sirtuins in aging and disease. Trends in cell biology, 24(8), pp.464-471.
Wątroba, M., Dudek, I., Skoda, M., Stangret, A., Rzodkiewicz, P. and Szukiewicz, D., (2017). Sirtuins, epigenetics and longevity. Ageing research reviews, 40, pp.11-19.