Unlocking the Secrets of Genetics: A Conversation with Prof Gasparini

Because I have always had a passion for research and the study of human genetics with its rules and its pathogenetic mechanisms. It has allowed me to cultivate this passion every day.

Epigenetics represents a fundamental branch of contemporary biology. It is at the center of scientific and medical discussions at this moment in history for several reasons:
 

1. Firstly, it offers a new level of understanding of how the environment and our lifestyle can influence gene expression. This is crucial because it allows us to better understand how external factors, such as diet, stress, pollution, and the social environment, can contribute to human disease and well-being.
2. Secondly, epigenetics is revolutionizing our understanding of nongenetic inheritances, opening new avenues for research on inherited diseases and the transmission of biological information from one generation to the next.
3. Lastly, this discipline also offers potential opportunities in the field of personalized medicine, where understanding epigenetic modifications can help develop targeted and individualized treatments. 
    

In summary, epigenetics is important because it helps us connect our environment, our lifestyle, and our health, opening new perspectives for disease prevention and treatment. It also gives us a better understanding of the biological mechanisms that drive our existence.

External factors can influence the expression of our genes and, consequently, our health status. This phenomenon is widely studied in the field of epigenetics, a discipline that focuses precisely on the chemical changes that occur in DNA without altering its sequence. Some scientifically proven examples of how external factors can affect genes include:
 

• Diet: diet can change the activity of genes through epigenetic changes. For example, folic acid in some foods can affect DNA methylation, which is a major epigenetic modification, and this can have implications for health.
• Stress: prolonged exposure to stress can lead to epigenetic changes that affect the body's response to stress itself and may contribute to health problems such as anxiety and depression.
• Environment: exposure to toxic chemicals in the environment can cause epigenetic changes that increase the risk of developing diseases such as cancer.
• Exercise: regular physical activity can positively influence the expression of genes associated with cardiac health and metabolism, reducing the risk of cardiovascular disease and diabetes.
• Prenatal experiences: events that occur during pregnancy can impact epigenetic changes in the fetus, influencing its future health and susceptibility to disease.
• Age: aging itself is associated with epigenetic changes, which may explain why some diseases are more common in older people.
   

Understanding epigenetics is therefore important because it helps us identify potential intervention points to prevent or treat diseases, taking into account both genetic and environmental factors.

As we have already mentioned, stress can lead to epigenetic changes, such as DNA methylation or histone modification, which can affect gene regulation. Moreover, if prolonged, it can also negatively affect the immune system, making an individual more susceptible to infections and chronic diseases. All this then relates to the genetically determined predisposition to develop certain diseases, such as diabetes or heart disease. Importantly, not all people with genetic predisposition necessarily develop the disease, and development depends on a complex interaction between genetics, environment, and lifestyle.

The effect of air pollution on gene expression is a phenomenon that has been the subject of several recent scientific studies and suggests how exposure to airborne pollutants can cause epigenetic changes in human genes. 
 

This is due to:

• Rapid epigenetic changes: exposure to air pollutants such as fine particulate matter (PM2.5), nitrogen oxides (NOx), volatile organic compounds (VOCs) and others can lead to rapid epigenetic changes. These changes may include DNA methylation, changes in histones, and other epigenetic adjustments.
• Gene activation and suppression: these epigenetic changes can affect the activation or suppression of specific genes. Some genes related to the inflammatory response, immune system, and antioxidant defense may be inappropriately activated, while others involved in the regulation of cell growth and DNA repair may be suppressed.

Air pollution is part, like diet and physical activity, of what we call the "environment," and is therefore a factor that can affect the expression level of some of our genes and thus be linked to premature aging.
 

There are no "definitive" studies yet on these mechanisms impacting long-term aging. However, some studies on prolonged exposure to air pollution have speculated that it may have negative effects, for example, on the appearance of the skin.
 

The mechanisms may be different:

• Oxidative stress: air pollution contains harmful chemicals, including fine particles, heavy metals, and volatile organic compounds. These substances can cause oxidative stress in the skin, which results in damage to skin tissue and contributes to premature aging.
• Inflammation: constant exposure to air pollutants can trigger chronic inflammatory responses in the skin. Chronic inflammation is known to accelerate the aging process and can cause wrinkles, hyperpigmentation and other signs of skin aging.
• Collagen degradation: air pollution can also contribute to the degradation of collagen, a protein that keeps skin young and supple. Loss of collagen can lead to flabby skin and more noticeable wrinkles.
• Free radical formation: air pollution can generate harmful free radicals that damage skin cells and contribute to premature aging.

Skin like any other tissue can be studied to better understand what genetic risk factors may influence its health status. This could include looking for genes associated with skin elasticity, collagen production, and UV sensitivity.

With the genetic information available, it will then be possible to assess individual susceptibility to specific skin problems, such as premature aging, tendency to wrinkles, or susceptibility to UV damage. Based on the results of the genetic analysis and individual predisposition, it is possible to offer personalized and targeted skincare.
 

Biological age is a measure that tries to assess how much a person has aged biologically, comparing it to his or her actual age. In other words, it represents how much a person's body has aged at the cellular and molecular levels. It can be different from one’s actual age because people age in different ways based on various factors, including genetics, lifestyle, environment, and general health.
 

There are a number of biological indicators, such as:

• DNA analysis, which can detect epigenetic changes, such as DNA methylation, which can change with age and affect gene expression.
• Telomeres, which are the ends of chromosomes that protect DNA. These get progressively shorter with age, so their length can be used as an indicator of biological age.
• Protein markers, certain proteins in the body can be used as markers of biological age. For example, the concentration of certain proteins in the blood can change with age, such as C-reactive protein (CRP) often used as an indicator of inflammation in the body.
• Certain general health parameters, such as blood pressure, heart function, bone density and others, can also be assessed to determine biological age.
   

At present, the incidence of these factors has been demonstrated in animal models, while in humans, who have a long life expectancy and do not live in a controlled environment, there are mostly observational or population studies.

That is why, in general, biological age is calculated by combining data from the different biological indicators and comparing them with a reference model based on a comparison population. The goal is to obtain an indicator that can be correlated with biological age that reflects how well or how poorly a person's body has aged, in comparison to his or her actual age. Right now these measures can be a way to track our changes.

Genetics plays an important role in determining our physical characteristics, metabolism and potential susceptibilities to certain health conditions. Knowing our genetic predispositions is important because it gives us information about our biological basis and what areas might need more attention. 
 

One example is the ACTN3 gene, which is involved in the production of a protein, alpha-actinin-3, associated with fast muscle fibers responsible for strength and speed in muscle movements. There are two variants of this gene, one of which produces the protein. The presence of the variant that produces the protein has been associated with greater muscle capacity in terms of speed and power and is therefore more present in athletes who excel in power sports.

However, it is important to note that genetics is not the only factor that influences physical abilities; these are mainly influenced by training, nutrition, and lifestyle. Knowing genetics, environment, and perhaps other biomarkers allows us to be more targeted in structuring a nutrition plan.

Indeed, more and more studies are showing that environment and lifestyle play a key role in modulating gene expression. These epigenetic changes can be influenced by our lifestyle, surroundings, diet, stress, and other external factors.

This means that our daily lifestyle choices can have a significant impact on our health and appearance, regardless of the underlying genetics.

In essence while genetic predispositions provide a basis, the way we live is equally crucial. Knowing our genetic predispositions gives us initial guidance, but adapting our lifestyles according to environmental and epigenetic conditions is essential to maximizing our overall health and well-being.
 

Increasingly accurate personalization based on the study of the genome.