Differences in the Gut Microbiome and Immune Function in Male versus Female Centenarians
Why are there more female than male centenarians? The difference in life expectancy between men and women is well known and well explored. The long list of potential causative mechanisms all come with supportive evidence, but are incompletely understood at the detail level. In particular it remains unclear as to the relative importance of each these contributing factors versus all of the others. Here, researchers focus on differences in immune function and the composition of the gut microbiome in extremely old individuals. These are connected items, as the immune system gardens the gut microbiome by removing potentially problematic microbes, while those problematic microbes can induce chronic inflammation and dysfunction in the immune system.
Extreme longevity, particularly reaching the age of 100 years, is an exceptionally rare trait in the human population, exhibiting significant variations in prevalence between genders. Women generally exhibit greater survival rates than men across all age groups, including centenarians, with the gender gap in life expectancy ranging from 4.2 to 6.2 years. Genetic factors and immune responses play a crucial role in achieving longevity; however, there is limited information regarding the mechanisms that regulate the differences in biological aging between men and women.
A strong immune system is a key factor in determining lifespan, and sex plays an important role in its composition and activity. The sex-based diversity in immunity between males and females is regulated by several mechanisms, including X chromosome inactivation, mosaicism, skewing, and dimorphism in the expression of X chromosome-encoded genes, as well as regulatory genes on the Y chromosome. Generally, women exhibit stronger innate and adaptive immune responses than men.
An additional factor that may contribute to gender differences in the immune system is the gut microbiota. Composition of gut microbiota varies between males and females providing sex-specific differences in immune responses. Notably, it has been demonstrated that the ratio of bacterial cells to human cells differs between males and females, with a ratio of approximately 1.3:1 for males and 2.2:1 for females. However, the mechanisms by which the gut microbiome contributes to conditions conducive to successful aging remain unclear. Consequently, future research should prioritize investigating the causal relationship between sexually dimorphic immunity and the microbiota.