Transposable element expression is associated with sex chromosome number in humans

Why women live longer than men is still an open question in human biology. Sex chromosomes have been proposed to play a role in the observed sex gap in longevity, and the Y male chromosome has been suspected of having a potential toxic genomic impact on male longevity. It has been hypothesized that transposable element (TE) repression declines with age, potentially leading to detrimental effects such as somatic mutations and disrupted gene expression, which may accelerate the aging process. Given that the Y chromosome is rich in repeats, age-related increases in TE expression could be more pronounced in males, likely contributing to their reduced longevity compared to females. In this work, we first studied whether TE expression is associated with the number of sex chromosomes in humans. We analyzed blood transcriptomic data obtained from individuals of different karyotype compositions: 46,XX females (normal female karyotype), 46,XY males (normal male karyotype), as well as males with abnormal karyotypes, such as 47,XXY, and 47,XYY. We found that sex chromosomes might be associated to TE expression, with the presence and number of Y chromosomes particularly associated with a global increase in TE expression. This tendency was also observed across several TE subfamilies. We also tested whether TE expression is higher in older males than in older females using published human blood transcriptomic data from the Genotype-Tissue Expression (GTEx) project. However, we did not find increased TE expression in older males compared to older females probably due to the heterogeneity of the dataset. Our findings suggest an association between sex chromosome content and TE expression and open a new window to study the toxic effect of the Y chromosome in human longevity.