Sirtuin Genes: What Role Do They Play in Anti-aging?

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Role of Sirtuin in Enhancing Longevity


It is a fact that people in today’s world live much longer that those who did centuries ago. For example, an estimate has it that average human life expectancy has increased by double, or more, since the 1800s. The search to extend lifespan even further continues despite this. We have seen many techniques or approaches that have been put forward for achieving longevity. Sirtuin genes are among those things that have been cited researchers as possibly holding the secret to aging. What is known about them and how can they be beneficial for promoting longevity?

About Sirtuin

The term “sirtuins” refers to a class of proteins present in living organisms. They are said to be proteins (or genes) that produce mono-ADP-ribosyltransferase or deacylase activity. Described as the “housekeeping genes,” sirtuins are believed to play vital roles in many important cellular processes in living organisms. The biological processes they help with include aging, apoptosis (programmed cell death), inflammation, and transcription. They regulate the activity of genes that are responsible for functions such as cell defense and metabolism.

These proteins control key biological pathways in archaea, bacteria and eukaryotes. It is thought that bacteria and archaea encode just a couple of sirtuins. But by contrast, eukaryotes are known to encode multiple of these proteins in their genomes.

For sirtuins to perform their functions, they usually need to be activated. Research shows that calorie restriction, reduction in your calorie intake, is an effective means of activating these genes. Experts think the ability of CR to deal with effects of aging may be explained, at least in part, by how it helps to activate sirtuins.

Types of sirtuins

Researchers have identified seven types of sirtuins in mammals. These are:

  • SIRT1
  • SIRT2
  • SIRT3
  • SIRT4
  • SIRT5
  • SIRT6
  • SIRT7

These proteins can be mostly found in nuclear, mitochondrial or cytosolic compartments in the body.

Of the different types, SIRT1 (also known as Sir2 in yeast) is the one that has most research done on it. It was the first to be identified, as its name suggests. It has received the most attention in terms of how sirtuins can help guard against age-related diseases and promote longevity. But the roles of other genes, especially SIRT3 and SIRT6, in these regards have been highlighted as well.

How can Sirtuins Help With Aging?

Sirtuins appear to alter the chemistry of your body to help combat aging. A major means by which it may extend your life is through effects on your DNA. This human hereditary material is enclosed in structures known as histones, which provide stabilization. When sirtuins are activated, this causes the DNA to be compressed on the histones. This reduces the rate of chromosome proliferation, thus helping to guard against errors.

Research shows that SIRT1, SIRT6, and SIRT7 are especially vital for DNA repair. SIRT1 facilitates homologous recombination to enhance correction of DNA defects. SIRT6 performs similar function and is crucial for mending DNA double strand breaks. SIRT7 also helps with double-strand break repair, and its absence has been shown to cause premature aging in mice studies.

Sirtuin can help to prevent or slow the onset of a variety of age-related medical conditions. These include the following:

Alzheimer’s disease

It is well know that there is a correlation between neurodegeneration and aging. Age-related decline in the function of the central nervous system is arguably one of the most troubling. Alzheimer’s disease is also probably the most fearsome of the kinds of neurodegeneration that are common among older individuals. Estimate has it that affects some 35 million people across the globe. It is a major cause of dementia in older individuals.

There is no known treatment for now to completely eliminate AD. But sirtuins are being studied as an option that may help in dealing with this awful condition. Using mouse models, researchers have observed that knockout of SIRT1 in the brain led to a considerable rise in beta-amyloid plaques and reactive gliosis, factors in the onset of this condition. Overexpression of the sirtuin protein, on the other hand, helped to improve the risk factors. SIRT1 is also believed to be beneficial in managing Huntington’s disease.

Metabolic dysfunction

The risk of metabolic syndrome, obesity and insulin resistance becomes greater as people get older. Researchers have attributed this to falls in the level of physical activity and basal metabolic rate. Multiple studies revealed that sirtuins, especially SIRT1, may help prevent these issues. Increase in the amount of these proteins, as a result of calorie restriction, causes certain enzymes and transcription factors to be deactivated.

The implication of SIRT1 actions is that it may help promote weight loss and fight diabetes, among other conditions. Studies have revealed that mild overexpression of the protein in mice placed on a high-fat diet led to considerable decline in plasma insulin and blood sugar levels. There was also no drastic change in body fat content.

There is also evidence that SIRT2 can assist in regulating the development and function of adipose tissue. It does this through deacetylation of transcription factors, particularly those of the FOXO family. This is why it is thought potentially helpful in guarding against obesity.

Cardiovascular disease

The elderly make up the group of people at higher risk of suffering cardiovascular disease. The condition is associated with heart and vasculature tissue deterioration. Other factors such as metabolic disorders, inflammation and oxidative stress can worsen the wear and tear that is experienced as a result of age. Activation of sirtuins, scientists believe, may help to prevent or slow the progression of cardiovascular disease associated with aging.

Endothelial cell function could be safeguarded through activation of SIRT1 in endothelial tissues, according to research. Low levels of the protein put you at risk of atherosclerotic lesioning and increased cell foam formation. It needs to be noted that effects you experience from SIRT1 activation depend on the level of increase in activity, though. Low to moderate overexpression is beneficial, but overexpression at higher levels may predispose a person more to developing cardiovascular issues.

SIRT 3 and 7 have also been identified among sirtuins that may help enhance your heart health. The former is thought useful for guarding against cardiac hypertrophy and mitochondrial dysfunction in older individuals. Evidence from mice study indicates that low SIRT7 levels could result in heart hypertrophy which may lead to death. It targets the tumor protein p53, whose activation causes greater programmed cell death in the myocardium.


Researchers think sirtuins also play a role in the development of cancers. What is not entirely clear here, however, is whether its effect is positive or otherwise. Some research indicates SIRT1 to be a tumor suppressor that may help with some types of cancer, including mutant breast cancer 1. Its overexpression interferes with the growth of fibro sarcoma cells.

However, some other studies show that sirtuins may in fact be a contributor to the development of cancer. High SIRT1 expression was observed in a variety of cancers, including colon carcinomas, prostate cancers, and acute myeloid leukemia. Reduction in the activity of the protein is therefore thought potentially helpful in promoting cancer cell death.

There is need for further studies to have a clearer idea of how sirtuins may impact people with cancer.

Some Foods that Activate Sirtuins

Calorie restriction is generally accepted as the principal activator of sirtuin genes. But there are also natural and artificial activators of the proteins. The natural activators are basically foods, while the artificial are drugs, which are capable of causing anxiety.

The natural activators are safer for those who may be interested in tapping into sirtuins’ potential benefits. These are foods aptly described as “sirtfoods.” They are mostly what you will find in average Asian and Mediterranean diets. In other words, these foods are the kinds usually recommended for the health-conscious. A “MeditterAsian” diet can protect against age-related chronic diseases and facilitate healthy aging. This is according to a research article in the journal Oxidative Medicine and Cellular Longevity.

The following are a few of the sirtfoods you may include in your diet to activate sirtuins naturally. You may already be consuming these if you are the type that makes effort to maintain a healthy diet.

Great tea – Rich in powerful antioxidants (especially catechins), green tea is getting more and more popular. It offers diverse health benefits, including protection against Alzheimer’s disease, prevention of cardiovascular disease, and promotion of weight loss. These benefits are probably the result of how it activates sirtuins. The nutrients you get from it include folate, B vitamins, and potassium.

Red Grape – This tasty fruit helps to activate sirtuins, particularly SIRT1, because of the presence of resveratrol. This compound is found in many plants, but it is mostly found in the skins of red grapes. Red wine, therefore, offers a great means of getting it. Resveratrol is now being promoted by some as the real deal in anti-aging. It helps to address factors that predispose a person to cardiovascular disease, a leading cause of death in many countries.

Fish – Oily fish is a common feature of both Asian and Mediterranean diets. This is a rich source of Omega-3 fatty acids. Reported incidence of cardiovascular disease is lower among people who eat fish rich in Omega-3 fatty acids. Tuna, salmon, sardines, and bluefish are some of the fish that you can consider for inclusion in your diet.

Olive oil – This offers oleuropein and hydroxytyrosol, properties that can promote healthy aging. Research shows that olive oil phenolics, such as hydroxytyrosol, caused reduction in oxidative damage markers. They also improved cardio protective proteins and are thought capable of inducing SIRT1 signaling.

Onions – These have long been used to deal with a variety of infections. Their total polyphenol content is greater than that of similar vegetables, such as garlic. The polyphenol quercetin may help to activate SIRT1. Red onions are best for this purpose. Chromium present in the bulb also assists in managing blood sugar levels. Onions boasts a wide range of organic sulfur compounds that offer a variety of health benefits. They are most beneficial when eaten raw.

Other sirtfoods that you can consider include parsley, kale, seaweed, soy, turmeric, and blackcurrants.

Sirtuins show great promise in helping to slow aging and preventing age-related diseases. Their activation may help to deal with pathological alterations that are seen in older people. The expectation is that further studies will shed more light on the benefits of these proteins. This, it is hoped, will be helpful in developing potent drugs. For now, sirtfoods may be relied on for activation of sirtuins to enjoy their benefits. But care needs to be taken not to consume these foods in excess.

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