Investigating telomere length in progeroid syndromes: implications for aging disorders.

Abstract

Progeroid syndromes are rare genetic disorders that impact patients' health and lifespans and are characterized by symptoms that mimic the normal aging process. Telomere length is one of the aging hallmarks, a phenomenon linked to cellular aging. Telomere attrition was observed in different progeroid syndromes, such as Nijmegen breakage syndrome patients and Werner syndrome, indicating its contribution to the progeroid phenotype. However, whether it is a common feature in all progeroid syndromes is still unclear. Therefore, in this study, we aimed to estimate telomere length using the DNA methylation-based estimator of human telomere length in publicly available DNA methylation data from patients with Werner Syndrome, Hutchinson-Gilford Progeria Syndrome, Berardinelli-Seip Congenital Lipodystrophy type 2, and Dyskeratosis congenita, along with additional data provided by our laboratory from patients with Cerebroretinal Microangiopathy with Calcifications and Cysts and Wiedemann-Rautenstrauch Syndrome. Our findings revealed that certain progeroid syndromes, including classical Werner Syndrome, Berardinelli-Seip Congenital Lipodystrophy type 2, and Dyskeratosis congenita, have significant telomere attrition conversely to Hutchinson-Gilford Progeria Syndrome, Cerebroretinal Microangiopathy with Calcifications and Cysts, Wiedemann-Rautenstrauch Syndrome, and atypical Werner Syndrome. In conclusion, this study addresses a critical gap by providing new insights into the role of telomere attrition across different progeroid conditions. Further research is needed to elucidate the effect of telomere attrition on progeroid syndromes and its implications.