Molecular Aging Markers in Patients with Klinefelter Syndrome

Abstract

Molecular aging markers provide the opportunity for biological age determination in humans and to study factors, such as genetic determinants, affecting the ageing process. In males with Klinefelter syndrome (KS, non-mosaic karyotype 47, XXY), which is the most common sex chromosome aneuploidy, age-related morbidity and mortality are increased, and a significantly reduced life span has been observed. The aim of this study was to investigate whether Klinefelter patients exhibit molecular signs of premature ageing. We studied, specifically, age-associated DNA methylation patterns (by pyrosequencing) and relative telomere length (TL; by quantitative polymerase chain reaction) in blood in a cohort of Klinefelter patients (n=178 and 266 for DNA methylation and TL, respectively) aged 18-71 years and compared them to the data of age-matched healthy male (n = 184 and 196 for DNA methylation and TL, respectively) and female controls (n = 50). Age-associated DNA methylation patterns were not indicative of accelerated ageing in Klinefelter men. Significantly longer telomeres were found in the young Klinefelter subjects aged 18-24 years (mean=1.51 vs. 1.09 and 1.26 in female and male controls, respectively). However, telomere length in subsequent age groups showed no difference to controls. Gonosomal aneuploidy in Klinefelter syndrome is associated with higher baseline TL at adolescent age, but comparable TL with progressive age in other age groups.

Disorders of sexual development associated with sex chromosomes: an update

“…Además, se ha reportado que individuos con ST o SK pueden presentar el mismo cariotipo pero exhibir rasgos completamente diferentes, lo que sugiere que no existe una relación convencional genotipo-fenotipo. (72)(73)(74)(75) Sin embargo, para entender el fenotipo resultante de las aneuploidias de los cromosomas sexuales en los pacientes con ST y SK, se requiere de más investigación para dilucidar la relación entre los genes, factores transcripcionales y mecanismos epigenéticos que afectan la expresión génica en todo el genoma, ya que se ha planteado la hipótesis de que estos síndromes están asociados a redes genéticas. (56,76) Manotas et al, mediante un análisis bioinformático in silico, lograron identificar 16 genes expresados diferencialmente entre pacientes con ST y SK de los cuales 14 están ubicados en el cromosoma X y 2 en cromosomas autosómicos.…”