Slowing down ageing is possible and research looks at telomeres

Why do we age? This is a crucial question for medicine and for our society, especially in Italy with its progressively ageing population. The question we can now answer is that we age because the cells in our bodies age. Over time, many of them stop dividing and enter a state called cellular senescence. This phenomenon prevents cells from proliferating and contributing to the normal replacement of damaged and dead cells. However, when a cell becomes senescent, it poses a problem not only for itself, but for the entire organism: it releases inflammatory signals and molecules that alter the surrounding cellular environment, damaging tissues and contributing to the development of chronic diseases typical of old age, such as fibrosis, cardiovascular diseases and even cancer.

Ageing, therefore, is not just a matter of time passing, but an active and regulated biological process. For centuries we considered it inevitable. Today, however, we know that ageing is regulated by well-defined molecular circuits, which means that we can study, understand and even modulate it. In other words, ageing is not just an entropic process of deterioration, but a phenomenon that can be slowed down or even counteracted through targeted interventions guided by scientific knowledge.

This realisation radically transformed ageing research, paving the way for geroscience, the discipline that studies the biological mechanisms of ageing by aiming to slow down, stop or reverse aspects of biological ageing in order to prolong life and maintain good health. The discovery that marked a breakthrough in this field came decades ago from a small worm with a particularly stylish shape and therefore called Caenorhabditis elegans: a simple genetic mutation was enough to double its life expectancy. Subsequently, studies in various animal species, including mammals, showed that the same pathways regulating ageing are also present in more complex organisms, including the human organism. These discoveries fuelled a growing interest in strategies to intervene in ageing at the cellular and molecular level.

But how can we do this? If we age because our cells age, we need to understand why they age. In our research group at Ifom and the CNR, we discovered that there is one part of our DNA that is particularly vulnerable: telomeres, the ends of our chromosomes. When telomeres become shortened or damaged, the DNA cannot be repaired, which leads the cell to age irreversibly.

In our laboratory, we have developed an RNA-based technology capable of inhibiting the molecular alarm signal that induces cellular ageing from damaged telomeres. We have tested these drugs on models of age-related diseases with very promising results. From this research was born Tag Therapeutics, an innovative start-up dedicated to the development of therapies for age-related diseases. One of our first applications concerns pulmonary fibrosis, for which we have already demonstrated efficacy in preclinical animal models.