Endocrine Abstracts

JOINT887

The sex chromosome aneuploidies Turner syndrome (45,X; TS) and Klinefelter syndrome (47,XXY; KS) are associated with aging-related comorbidities, reduced life expectancy and genome-wide DNA methylation changes. The objective of this study was to investigate whether the aging-related comorbidity pattern and the reduction in lifespan was associated with epigenetic aging. We assessed epigenetic age and age acceleration using six different epigenetic clocks predicting chronological age, phenotypic age, aging pace and telomere length. DNA methylation was obtained from existing cohorts of TS (TS, n=47; female controls, n=33) and KS (KS, n=65; male controls, n=63). In addition, we evaluated correlations between epigenetic aging and clinical variables, aiming to identify clinical aging markers in TS and KS. Epigenetic age and age acceleration based on predictors of chronological age were increased in both TS and KS compared to respective controls (P<0.015). Epigenetic age and age acceleration based on predictors of phenotype were increased in TS (P<0.019), as well as aging pace (P<0.001). Telomere length was decreased in TS (P<0.001) and slightly increased in KS (P=0.06). Markers of body composition and muscle mass were correlated to age acceleration in TS, while these traits were correlated to chronological and epigenetic age in female controls. Similarly, markers of body composition were more consistently correlated to aging pace in KS than male controls, while an age-dependent increase in triglyceride levels and body fat percentage seemed to be diminished in KS. We demonstrated that biological aging was clearly increased in TS and, to some extent, in KS. This could explain some of the excess mortality observed in these syndromes. Additionally, unfavorable changes in body composition, which are common in both syndromes, particularly if left untreated, could result in accelerated aging – or be the result hereof.