Paolo Sassone-Corsi, a professor of Biological Chemistry at the University of California, Irvine, is working on studying the rhythms that regulate our biology in order to shed light on behaviors that are hazardous to health and should be avoided, but also to understand how to make drug treatments more effective. He is one of the first scientists to investigate how the environment influences gene function without it changing the DNA sequence. In an interview with the Aspen Italia website team reproduced below, Sassone-Corsi discusses how his research is exploring the molecular mechanisms that link the day-night cycle and nutrition to cellular metabolism, and, hence, to epigenetics. These studies, of both medical and social significance, are enabling the development of new pharmacological strategies for diabetes, obesity, metabolic syndromes, and drug addiction.
The mystery of epigenetics: what is the explanation for changes that vary gene expression without affecting the DNA?
DNA itself does not change during a person’s lifetime, yet DNA is found in all our cells, despite them having very different functions. So how is it possible? The answer is thanks to the epigenome, something which – as the Greek prefix “epi” suggests – sits on top of the genome and can modify gene expression without altering the DNA sequence. External factors such as drugs, high levels of stress, depression, but also bad eating habits, have a strong influence on the epigenome. The intensity of these effects depends on their frequency and their recurrence over time. Changing time zones too often, always eating late at night, or gorging on hamburgers everyday are behaviors that affect the epigenome, and the more they accumulate, the more they become irreversible.
What, in substance, are the effects of this process?
The impact of certain behaviors on the epigenome not only leads to the onset of diseases in the individual, but also increases the possibility of hereditary transmission of such diseases. A case in point is diabetes, which in most cases affects people with nutritional problems. It isn’t a genetic disease, because there is no change in the DNA, yet this disease can occur in the offspring of an affected person. How can this be seeing as the DNA doesn’t change? Such transmission can be explained by changes in the epigenome which, in some instances, can be transmitted from generation to generation. In short, there are factors that increase the susceptibility of offspring to a disease acquired from parents. There is a need for further research to better clarify the mechanisms at play, but the potential is considerable, because although it hasn’t proved possible to repair the DNA, at the epigenome level there is the possibility of therapeutic intervention.
How much of a contributing factor are our eating habits?
Nutrition is closely linked to our biological cycles. Think of a simple experiment in which you take two guinea pigs that are exactly alike, with the same DNA, and you give them the same food to eat over two months. One of them is given food at the right times, and the other is fed at different and “wrong” times. By the end of the experiment, the latter will have become fatter.
This is because it’s not just how much you eat that’s important, but also when you eat. We’ve discovered that 50% of our metabolism is circadian, that is, it is reliant on 24-hour cycles. There are thousands of metabolites in our body regulated by circadian cycles which contribute to homeostasis of the body itself. These cycles dominate our lives and absolutely all our metabolic functions. So by eating a hamburger at 3 in the morning, we put stress on our metabolism, and if this disruption of the circadian cycles becomes habitual, serious problems can arise.
What advances could the study of circadian rhythms make possible?
These cycles – whose name derives from the Latin circa diem, meaning “about a day” – are the oldest element of life on our planet, which has developed not just by adapting, but thanks precisely to this marking of time. The molecular system that regulates our rhythms has been preserved during evolution and, hence, circadian cycles are intrinsic to our biology. Understanding these mechanisms enables us not only to study the negative effects of certain lifestyles, but also to develop a pharmacology and therapeutic approaches that are time-specific. It is what we call “chrono-pharmacology”: if we know at what time to administer the proper medication, it can be much more effective. This way, we can ensure improved absorption by the body, and thereby optimize the effect of a molecule.
