Sirtuins: The "Longevity Genes" You Need to Know About

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Sirtuins: The

There's a very good reason that sirtuins are often referred to as our "longevity genes" -- they affect multiple cellular pathways that increase the lifespan and the overall health of organisms, including humans.

In mammals, the sirtuin family consists of seven proteins. They regulate cellular health, and play a vital role in regulating cellular homeostasis. Homeostasis involves keeping cells in balance, but sirtuins can only help do this if they are aided by NAD (nicotinamide adenine dinucleotide), a coenzyme found in all living cells.

Of the seven sirtuins in our cells, three of them work in the cells' mitochondria, known as the powerhouses of the cell. These mitochondria are organelles that act like a digestive system which takes in nutrients, breaks them down, and creates energy-rich molecules for the cell, a biochemical process known as cellular respiration. Another three sirtuins work in the cell's nucleus (containing the majority of the cell's genetic material), and one of them works in the cytoplasm (a thick solution mainly composed of water, salts, and proteins that fills each cell and is enclosed by the cell membrane).

Each sirtuin plays a variety of roles, but the basic role of sirtuins is to regulate gene expression in a manner that can improve our longevity and health.

The Most Studied Sirtuins

Sirtuin enzymes enable our longevity genes to help support healing and well-being.

We've only known about the role sirtuins play in aging for about 20 years, beginning with research on yeast, where researchers found that increasing the second sirtuin, called SIRT2, resulted in extending the life span of yeast. Later, these same effects were replicated in worms and fruit flies. It became clear to scientists that sirtuins are found across species and have been "conserved" throughout evolution. Genes that are "conserved" have universal functions in many or all species. What was yet to be known, though, was how important sirtuins would turn out to be.

Of the seven sirtuins found in mammals, SIRT1 has been of most interest to researchers, because it is closest to SIRT2 (the sirtuin that enabled lifespan increases in yeast, worms and fruit flies) in structure and function. What has become clear to researchers is that sirtuins regulate a diverse group of cellular functions in mammals. SIRT1 may prove to have important clinical possibilities in the management of diabetes, cancer, cardiovascular disease, and neurodegenerative disease. But SIRT1 may not be the most important sirtuin gene for promoting human longevity -- SIRT6 is slowly gaining recognition as well.

Researchers first determined that mice that lacked the SIRT6 gene seemed to age faster. They were smaller and more prone to disease. They also had a reduced ability to repair damaged DNA and died about a month after birth, on average. The researchers wondered what would happen if their test animals had higher than normal levels of SIRT6. This was tested and resulted in the female mice being unaffected, but the lifespan of the male mice rose by as much as 14.5%. The reason this might have happened, the researchers speculated, is because females live about 15% longer in this particular strain of mice, and the SIRT6 simply allowed the males to catch up with the females.

What all this means for us humans has yet to be discovered. What is evident from the research is that sirtuin activation may soon be a potent resource in anti-aging medicine.

You Need NAD to Activate Sirtuins

NAD (nicotinamide adenine mononucleotide) is directly involved in activating sirtuins, as they require healthy levels of NAD to function optimally. Therefore, if we are to benefit from increased sirtuin activity, we should increase our NAD levels.

The best way to increase NAD is with the NAD precursors, NMN and NR (nicotinamide mononucleotide and nicotinamide riboside). Sirtuin activation has also been linked to supplementation with resveratrol (particularly a form called trans-resveratrol) and quercetin, as well as caloric restriction.

Caloric restriction has been shown to protect against age-related diseases, made evident by how this practice changes the levels of biomarkers for type II diabetes, hypertension, cardiovascular disease, cancer and dementia. Scientists believe that sirtuins help mimic the beneficial cellular effects of caloric (dietary) restriction:

Your Sirtuin Takeaway

It seems clear that sirtuins play a key role in supporting cellular integrity and healthy DNA. We also know that optimal sirtuin expression requires the presence of a robust amount of cellular NAD, something that might be achieved by NAD precursors, such as NMN and NR.

Show references

Grabowska W, Sikora E, Bielak-Zmijewska A. Sirtuins, a promising target in slowing down the ageing process. Biogerontology. 2017;18(4):447-476. doi:10.1007/s10522-017-9685-9

Guarente L, Picard F. Calorie restriction--the SIR2 connection. Cell. 2005;120(4):473-482. doi:10.1016/j.cell.2005.01.029

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;13(19):2570-2580. doi:10.1101/gad.13.19.2570

Kanfi, Y., Naiman, S., Amir, G. et al. The sirtuin SIRT6 regulates lifespan in male mice. Nature 483, 218-221 (2012). doi: 10.1038/nature1081

Wenzel U. Nutrition, sirtuins and aging. Genes Nutr. 2006;1(2):85-93. doi:10.1007/BF02829950

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