Gender differences in oxidative and inflammatory parameters linked to ageing

In this review article, the Spanish authors discussed the gender-specific differences in several markers of ageing to shed more light on the differences in ageing and life expectancy between genders. They focused on oxidative and inflammatory processes, and gender differences in oxidative and inflammatory parameters linked to ageing in both human and murine models.

The metabolism changes with age, showing an increase in glycolysis and the production of reactive oxygen species (ROS), and a reduction in mitochondrial synthesis. The “oxidative-inflammatory theory of ageing” suggests that the general decline in function experienced with age is the result of the establishment of both chronic oxidative and inflammatory stresses in the body. The leakage of ROS from mitochondria and ROS produced by oxidant enzymes over time creates an oxidative stress situation. This process, persistent over time, damages mitochondrial and nuclear DNA, proteins, and lipids in all body cells. However, there are opinions opposed to the “free radical theory of ageing” based on studies in which the use of antioxidants did not increase longevity.

Additionally, the process of immunosenescence modifies the immune response leading to a variety of diseases, such as tumors and infections. The immune system senescence reflects the senescence of different subpopulations of cells of the immune system. During aging, the cytotoxic activity of immune cells declines, while the expression of functional molecules associated with cytotoxic activity, such as interferon-gamma, granzyme B, and perforine, is reduced.

Women generally live longer than men, which corresponds to the lower biological ages assessed by different molecular biomarkers. The increased longevity of women is also observed in other species.

The accumulation of age-related oxidative damage has been described to occur more slowly in women from puberty to menopause, due to the antioxidant action of estrogens. However, the depletion of estrogens in women after menopause increases oxidative stress, generating oxidative damage and consequently accelerating the rate of ageing in elderly women.

About the study

The authors analyzed gender-specific differences in redox parameters. It is generally thought that males have more oxidative stress than females. This has been observed in many species, including flies, mice, rats, and humans. The authors summarized the main differences between the genders in the parameters of oxidative stress and markers of oxidative damage: production of ROS, antioxidant defense mechanisms, and markers of oxidative damage such as protein damage, lipid damage, and oxidative damage to DNA.

They also discussed gender-specific differences in inflammatory markers such as the number of immune cells, pattern recognition receptors, toll-like receptors, NOD-like receptors, as well as immune soluble factors. In addition, the scientists explained the important role of circulating cell-free DNA as a marker that links oxidation and inflammation, and has the potential to become a useful ageing marker.

The investigators also analyzed the way in which oxidative and inflammatory changes occur differently with ageing in each gender. This may have an impact on a differential lifespan of each gender, as males exhibit, in general, higher oxidation and a basal inflammation.

Finally, ageing is characterized by immunosenescence resulting in a higher incidence of infections, an attenuated response to vaccines, and an increase in morbidity and mortality. The senescent microenvironment is strongly associated with tumor metastasis and invasion. Although both genders experience age-related changes in the immune system, males have been considered to experience these changes at a more dramatic or accelerated rate.

The authors conclude that there is a need to continue research on gender differences in oxidative and inflammatory parameters linked to ageing. The scientists should include gender as an essential variable in order to understand the causes of gender-specific differences in ageing and ageing itself.

This article was published in journal Mechanisms of Ageing and Development. de Toda IM, et al. Gender differences in markers of oxidation and inflammation. Implications for ageing. Mechanisms of Ageing and Development 2023; 211: 111797. (Open Access)