Under stress, women’s cells resist, men’s cells “suicide themselves” – From “Medicine Highlights” for Il Mattino

Professor Antonio Giordano now contributes a dedicated column titled “Medicine – Highlights” to Il Mattino, one of Italy’s most esteemed and widely circulated daily newspapers, long-established as a cornerstone of Southern Italian journalism.

Below follows the content of the article as published in the Italian edition of Il Mattino.

Under stress, women’s cells resist, men’s cells “suicide themselves”

A recent study investigated how male (XY) and female (XX) cells respond differently to stress.

The research – published on Cell Death and Disease, revealed that male cells activate apoptosis—a form of programmed cell death or cellular “suicide”— while female cells instead trigger autophagy, a self-preservation mechanism that promotes survival under stress.

The focus of the research concentrated on the identification of the genetic factors that mediate these responses.

The researchers hypothesized, and subsequently demonstrated, that microRNAs (miRNA) small non-coding RNA molecules that regulate gene expression at the post-transcriptional level play a key role. In particular, miR-548am-5p was identified, whose differential expression between the two sexes is correlated with the activation of specific cellular pathways.

In female cells, exposure to stress induces the activation of the autophagy process, a catabolic mechanism essential for the maintenance of cellular homeostasis and survival in adverse conditions. Autophagy allows the cell to degrade and recycle damaged or non-essential components, providing energy and substrates for the synthesis of new macromolecules.

On the contrary, in male cells, the same stressful stimulus leads to the predominant activation of the apoptosis pathway, or programmed cell death. This process, finely regulated, is fundamental for the elimination of damaged or unnecessary cells, but in this specific context it indicates a lower resilience capacity compared to female counterparts.

Implications for personalized medicine and gender medicine.

These results underline the importance of considering the intrinsic biological differences between the sexes not only at the clinical level, but also in basic research. The identification of miRNAs as modulators of cellular responses to stress provides a solid basis for further investigations into the pathogenetic mechanisms of diseases that present different incidence or course between men and women, such as autoimmune or neurodegenerative pathologies.

The understanding of these molecular signaling pathways opens the way to the development of targeted and personalized therapies, capable of modulating the expression of specific miRNAs or of selectively intervening on the mechanisms of apoptosis and autophagy, with the aim of improving the efficacy of treatments. This study represents a significant step forward towards precision medicine that takes into account the biological sex of the patient.

Credits: This article was originally written in Italian for ilmattino.it​

Professor Antonio Giordano, M.D., Ph.D., is the creator and head of the Sbarro Health Research Organization

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