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Dr. Zajíčková: What really drives ageing and chronic diseases

What happens in your cells as we age: ROS, AGEs, telomeres and protein aggregation under the microscope of science

In modern populations, there is growing interest in understanding the basic biological mechanisms that influence health, ageing and the risk of chronic diseases. Today, it is no longer enough to know only about “calories” or “cholesterol” — if you want to apply science to everyday decisions, it is beneficial to learn new concepts. Examples include reactive oxygen species (ROS), advanced glycation end products (AGEs), telomeres, and protein aggregation. These mechanisms lie at the interface between cell biology and healthy prevention, and understanding them will allow you to better manage stress, nutrition and lifestyle with a long-term impact on your health. What do they actually mean and why should we care about them?

1. Reactive oxygen species (ROS)

ROS are highly reactive oxygen-containing molecules. They are a natural part of cellular metabolism and are essential for immune response and cellular signalling. However, I believe that the general public often does not distinguish between physiological ROS and oxidative stress, which occurs when there is an excess of ROS. The most well-known ROS include:

  • Superoxide anion (O₂·⁻) – a radical with a free electron, formed mainly in mitochondria during cellular respiration.
  • Hydroxyl radical (·OH) – one of the most reactive free radicals, can damage DNA, lipids and proteins.
  • Hydrogen peroxide (H₂O₂) – although not a free radical, it serves as a source of other ROS and can form even more reactive forms in the presence of transition metals.
  • Singlet oxygen (¹O₂) – an energetically excited form of oxygen with high reactivity towards cellular macromolecules.

ROS are a natural part of cells — they are produced during respiration, immune response and metabolism. However, their excess can cause oxidative stress — a condition where ROS production exceeds the body’s antioxidant defence mechanisms. This imbalance can lead to:

  • DNA damage, which promotes mutations and cellular ageing;
  • lipid peroxidation, which disrupts cell membranes and leads to inflammation;
  • modification of proteins, causing them to lose their function or aggregate;
  • The result is an increased risk of cardiovascular disease, diabetes and neurodegenerative diseases.

Preventing and eliminating excess ROS in practice means focusing on:

  • a balanced diet rich in antioxidants (vitamins C and E, polyphenols), which help neutralise free radicals;
  • regular physical activity, which improves the antioxidant potential of cells;
  • managing chronic stress and getting enough sleep, as stress hormones can promote ROS production;
  • reducing toxins (tobacco smoke, pollution) that increase oxidative stress in the body.

From the above, I would like to conclude that maintaining a balance between the production and elimination of ROS is one of the key pillars of chronic disease prevention.

2. Advanced glycation end products (AGEs):

AGEs are formed when sugars bind non-enzymatically to proteins, lipids or DNA. This process is toxic to the body because it modifies functional molecules and impairs their properties — for example, collagen in blood vessels or skin can lose its elasticity.

High blood glucose levels (e.g. in diabetes) are the main cause of increased AGE formation. I assume that most readers are unaware that heat treatment of food (e.g. baking or grilling at high temperatures) can also cause AGE formation.

From a prevention perspective, it is useful to limit refined sugars, maintain stable glycaemic control and favour gentle heat treatment when cooking. This approach not only reduces the body’s exposure to AGE products, but also promotes overall metabolic balance and healthy blood vessels.

3. Telomeres: the biological clock of cells and how lifestyle affects them

Telomeres are repetitive DNA sequences at the ends of chromosomes that protect genetic material during cell division. With each division, telomeres shorten — this is a natural process of ageing. However, if they fall below a critical length, the cell ceases to divide effectively, leading to senescence or apoptosis (programmed cell death).

In this topic, it is also appropriate to ask the question: “How does daily mental and physical stress affect the cellular nucleus?”

Chronic stress and unhealthy lifestyles affect telomeres through several biological mechanisms. Several studies and systematic reviews document that these effects are not just hypothetical, but have a clear scientific basis.

A systematic review analysing 56 clinical studies with over 113,000 participants showed that chronic psychological stress, including anxiety and depressive symptoms, is associated with shortened telomere length, with proposed mechanisms including oxidative stress and inflammation.

The latest meta-review published in Scientific Reports5 (2025) also summarises the negative association between depressive disorders (with accompanying stress) and telomere length, reinforcing the evidence that psychological stress can affect the biological ageing of cells.

4. Protein aggregation: link to neurodegeneration and cell health

Protein aggregation occurs when proteins fold incorrectly and form insoluble clumps. Such aggregates lose their function and can directly damage cellular mechanisms. This process is particularly problematic in the brain, where the accumulation of misfolded proteins is associated with neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s disease. Such aggregates disrupt communication between neurons and trigger inflammatory and oxidative reactions.

Preventing protein aggregation is not just theoretical. One way to do this is through regular physical activity, which improves cellular control of protein quality and reduces aggregation. This phenomenon was described in a 2018 study, which suggests that exercise may have a protective effect not only on muscles but also on mechanisms associated with protein aggregation-related diseases. Other preventive measures include: reducing oxidative stress, metabolic and energy balance.

Conclusion: why you really need to know about these mechanisms…

Although these are different mechanisms, the common denominator is oxidative stress, chronic inflammation and cell condition. ROS, AGEs, telomeres and protein aggregation are interconnected in a network of biological pathways that influence how quickly your body ages and how robustly it copes with the challenges of everyday life.

Therefore, investing in lifestyle — nutrition, exercise, sleep, stress management — is not just about “feeling better today,” but about how to influence these biological mechanisms towards a longer, healthier life.

I believe that such a practical and scientifically based understanding of biological processes can motivate lasting changes that have a real impact on health and open the door to a new generation of preventive approaches.

Ing. Mária Zajičková, PhD.
organic chemist, science populariser

1. Liguori, I., Russo, G., Curcio, F., Bulli, G., Aran, L., Della-Morte, D., … Abete, P. (2018). Oxidative stress, ageing, and diseases. Clinical Interventions in Aging, 13, 757–772. https://doi.org/10.2147/CIA.S158513
2. Sies, H., Berndt, C., & Jones, D. P. (2017). Oxidative stress. Annual Review of Biochemistry, 86, 715–748. https://doi.org/10.1146/annurev-biochem-061516-045037
3. Singh, R., Barden, A., Mori, T., & Beilin, L. (2001). Advanced glycation end-products: A review. Diabetologia, 44, 129–146.
4. Mashayekhi, F., Hashemi, S., & Mousavi, S. (2021). Telomere shortening and psychiatric disorders: A systematic review. Journal of Psychiatric Research, 137, 107–117.
5. Ismail, A., Chen, H., & Lee, J. (2025). Association between depression and telomere length: A systematic review and meta-analysis. Scientific Reports, 15, 10245.
6. Klaips, C. L., Jayaraj, G. G., & Hartl, F. U. (2018). Pathways of cellular proteostasis in ageing and disease. Journal of Cell Biology, 217(1), 51–63.

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