Accelerated telomere shortening in individuals with intellectual disability

Presentation


Hanley, Sarah M., Schutte, Nicola S. and Denham, Joshua. 2023. "Accelerated telomere shortening in individuals with intellectual disability." 18th Australian Cell Cycle, DNA repair and Telomere Meeting. Melbourne, Australia 23 Oct - 25 Nov 2023 Australia.
Paper/Presentation Title

Accelerated telomere shortening in individuals with intellectual disability

Presentation TypePresentation
AuthorsHanley, Sarah M., Schutte, Nicola S. and Denham, Joshua
Number of Pages1
Year2023
Place of PublicationAustralia
Web Address (URL) of Conference Proceedingshttps://australiancellcycle.org/program/
Conference/Event18th Australian Cell Cycle, DNA repair and Telomere Meeting
Event Details
18th Australian Cell Cycle, DNA repair and Telomere Meeting
ACDTM 2023
Delivery
In person
Event Date
23 Oct 2023 to end of 25 Nov 2023
Event Location
Melbourne, Australia
Event Venue
Melbourne Museum
Event Web Address (URL)
Abstract

Telomeres maintain genomic stability by safeguarding the chromosomes from DNA damage and fusion events. Telomere length and the rate of telomere attrition are important factors regulating health and lifespan. For instance, many age-related chronic diseases are linked to short dysfunctional telomeres.

Individuals with intellectual disability (ID) have intellectual quotients below 70 and suffer terrible health inequities compared to the general population. Indeed, they exhibit a higher prevalence of chronic disease and die prematurely. Here, we performed a systematic review and meta-analysis examining telomere length and telomere attrition in individuals with ID.

The cohort of 387 individuals with ID (diagnosed with either Down [DS], 5–p, Williams-Beuren, Nicolaides-Baraitser or Hoyeraal-Hreidarsson [HH] syndrome) possessed shorter telomeres than 505 age-matched healthy controls (SMD [95%CI]: -0.90 [-1.61–-0.19], p=0.01). An increased effect size was noted after the exclusion of infants (≤1 y with DS) (-1.59 [-2.28–-0.91], p<0.001). Furthermore, individuals with DS and HH exhibited a faster rate of telomere attrition compared to healthy controls (0.5–2.1-fold).

Regardless of the genetic heterogeneity of syndromes associated with ID, our findings suggest telomeres are, on average, shorter in patients compared to age-matched controls. While the genetic irregularities impacting telomere length in HH are obvious (e.g. DKC1, TERT, TERC, RTEL1 mutations), the genetic (gene dosage, rare mutations, etc) and environmental factors governing telomere length in other syndromes associated with ID should be investigated. This may uncover novel therapeutic strategies, including both pharmaceutical and tailored lifestyle interventions, aimed at improving the health and wellbeing of individuals with ID.

Contains Sensitive ContentDoes not contain sensitive content
ANZSRC Field of Research 2020310508. Genome structure and regulation
329999. Other biomedical and clinical sciences not elsewhere classified
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Byline AffiliationsDepartment of Education, Queensland
University of New England
School of Health and Medical Sciences
Centre for Health Research
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