Restricting a Single Dietary Nutrient Can Help Protect Against Cancer and Ageing
A balanced diet limiting specific nutrients is a tool that helps slow down the ageing processes, maintain good health, and prolong life. Accordingly, in the coming decade, researchers will focus on studying how specific dietary components – such as amino acids, carbohydrates, fats, and microbiota – affect our health and longevity.
Scientists will explore which food components contribute to chronic diseases or even cancer, and how these effects are linked to dietary restrictions, physical activity, and other healthy lifestyle elements. The long-term benefits of limiting specific individual nutrients have already been confirmed. Such diets may offer anti-cancer benefits, slow ageing, protect the cardiovascular system, and improve gut microbiota and brain health.
Health gains associated with methionine
Recently, protein consumption has garnered significant attention in online discussions, which may give the impression that it is the most crucial nutrient for the human body. However, this approach is misleading. To function properly, our bodies need proteins, carbohydrates, fats, vitamins, fibre, and water. To stay healthy and live longer, a proper balance of all these nutrients is essential, along with avoiding over- and under-eating.
Did you know that one of the most essential nutrients for our body is methionine, an amino acid found in proteins? It is vital for the proper development of the body. Simply put, methionine plays a key role in the body’s ability to produce proteins and maintain good health. It also helps combat inflammation and supports healthy tissue function.
Due to its importance for our metabolism and bodily functions, methionine is essential to the human diet. However, excessive intake of this amino acid through food can lead to many health issues, including atherosclerosis, short-term memory loss, neurodegenerative diseases, and reduced skeletal muscle growth. Therefore, it is advisable to consume methionine in moderation.
A methionine-restricted diet can prolong life
The discovery that long-term methionine limits can increase the lifespan of rats by up to 30% sparked extensive research into methionine-restricted diets. These studies have shown that reducing methionine intake also extends lifespan in other model organisms, such as Caenorhabditis elegans, fruit flies, and mice. This effect is associated with reduced production of reactive oxygen forms, higher levels of cellular antioxidants, and decreased oxidative damage to proteins, fats, and DNA.
Recently, more and more attention has been paid to methionine-restricted diets. This dietary approach can provide a range of benefits: it may offer anti-cancer effects, improve metabolism, slow ageing, stop inflammation, prevent diabetes, enhance insulin sensitivity, protect the cardiovascular system, and support gut microbiota and brain health.
Methionine is found in plant, animal, and microbial foods, but its concentration varies significantly across different food groups. The highest levels are found in meat, seafood, Brazil nuts, and eggs; moderate amounts are present in dairy products, while fruits and vegetables contain the lowest levels. The ketogenic, Japanese, and vegan diets tend to have the lowest methionine content. Given the wide variation in methionine levels across foods and different diets, there is a growing interest in developing a method for calculating and monitoring dietary methionine intake more precisely.
While methionine restriction offers considerable potential health benefits, it is still crucial to ensure an adequate intake of this amino acid, as too little of it can lead to growth disorders. Therefore, it is essential that the restriction of any nutritional element does not result in an overall deficient diet.
Methionine is a direct target for cancer treatment
An enzyme called methionine adenosyltransferase (MAT2A) produces an important molecule from methionine, known as S-Adenosyl methionine (SAM). This molecule is involved in the DNA modification process called DNA methylation. In basic terms, methylation occurs when a small part of this molecule – a methyl group – binds to DNA. If the body lacks methionine, SAM is not produced, so methylation cannot take place.
DNA methylation is an essential process that occurs in every human cell. It alters the structure of DNA, which often leads to specific genes being ‘switched off’, meaning they become inactive. This regulates essential processes in the human body, for instance, by ensuring the stability of genetic information. Methylation helps cells perform their unique functions in the tissue during development (e.g. allowing an embryonic stem cell to become a skin, liver, or nerve cell).
This process starts changing as we age: many genes lose their methylation marks, while others become heavily methylated. As a result, some genes critical to cellular function may stop working.
This mechanism of DNA regulation is also important in the case of diseases, particularly cancer. In cancer cells, some genes undergo extensive modifications that impair their function (even when that function is crucial), while others become active when they should not be. This imbalance in gene activity promotes the transformation of healthy cells into cancerous ones. For this reason, methionine – from which the SAM molecule is synthesised – is of significant interest in cancer research.
In fact, nearly 50 years ago, scientists discovered that cancer cells require more methionine from external sources compared to healthy cells. The more aggressive the cancer cells are, the more dependent they are on this amino acid to sustain their activity. Therefore, limiting it in food can be one of the new avenues for cancer treatment.
The levels of methionine in the body can be reduced in two ways: by following a special low-methionine diet or by using a protein called methioninase as a drug to break down methionine. Studies show that lowering methionine levels and simultaneously applying chemotherapy or radiotherapy can lead to better treatment outcomes.
Clinical trials are underway to investigate how limiting this amino acid affects cancer cells and their environment: immune cells, blood vessels, and connective tissue cells. However, many details still need to be clarified.
Vilnius University researchers develop a method for detecting epigenetic changes
Three key proteins operate in our bodies – DNA methyltransferases, also known as epigenetic ‘writers’ because they can ‘write’ the epigenetic code by modifying DNA, thereby altering the functioning of the cell. These enzymes are called DNMT1, DNMT3A, and DNMT3B. Two of them – DNMT3A and DNMT3B – create new ‘marks’ that determine a cell’s function, while DNMT1 ensures that these ‘marks’ are preserved and passed on to daughter cells during cell division. This process is crucial for normal development and health.
However, when the activity of these methyltransferases is disrupted, the consequences can be severe, triggering, for example, cancerous processes. In such cases, genes that should suppress tumours are ‘switched off’, while cancer-promoting genes become overly active. As a result, cells ‘forget’ their original function and turn malignant. These types of changes are found in many forms of cancer, including those affecting the blood, lungs, liver, and colon.
Until now, it has been challenging to study how each DNA methyltransferase works, but scientists at Vilnius University’s Life Sciences Center and the Faculty of Chemistry and Geosciences have developed a new method that allows researchers to precisely identify how each of these ‘writers’ affects DNA.
A breakthrough in research
Scientists have developed modified molecules capable of ‘tagging’ DNA in a way that reveals the activity of a specific enzyme. To deliver these molecules into cells, they used electroporation, a technique which temporarily opens up pores in the cell membrane using an electric field. These pores allow the modified molecules to enter the cell and ‘record’ information about DNA modifications.
Developed by researchers from Vilnius University, this method is the first in the world to easily and accurately distinguish the activity of the three methyltransferases under minimally invasive conditions and determine the specific effects of the DNMT1 enzyme. In addition, the scientists devised a less invasive approach by using chemically modified methionine analogues, i.e. molecules that easily pass through the cell membrane and are converted inside the cell into a modified SAM molecule. This enables the regulation of DNA modifications by altering the concentration of methionine in the cell environment. As a result, this method can be applied to detect epigenetic differences in cancer cells under methionine-restricted conditions.
It allows researchers to precisely monitor each methyltransferase's activity and better understand how epigenetic changes contribute to cancer development. Moreover, this technology can be used to study DNA changes in individual cells, tissues, and even throughout the body. It can be applied to various cancer models and used to study DNA, RNA, and protein modifications.
The new methodology represents a significant step forward in cancer biology research, offering a deeper understanding of the disease and potentially leading to more effective treatments in the future.
This research was supported by the Research Council of Lithuania (LMTLT), project No. MIP-23-108, “DNMT1-Selective DNA Methylation Mapping in Tumor Cells Using Preclinical Cancer Models”, and the Vilnius University Young Scientists’ Ideas Project, “Application of Cascade MAT2a-DNMT Genome Tagging Strategy in Cancer Cells”.