We have located links that may give you full text access.
Journal Article
Research Support, Non-U.S. Gov't
The polygenic nature of telomere length and the anti-ageing properties of lithium.
Neuropsychopharmacology 2019 March
Telomere length is a promising biomarker for age-related disease and a potential anti-ageing drug target. Here, we study the genetic architecture of telomere length and the repositioning potential of lithium as an anti-ageing medication. LD score regression applied to the largest telomere length genome-wide association study to-date, revealed SNP-chip heritability estimates of 7.29%, with polygenic risk scoring capturing 4.4% of the variance in telomere length in an independent cohort (p = 6.17 × 10-5 ). Gene-enrichment analysis identified 13 genes associated with telomere length, with the most significant being the leucine rich repeat gene, LRRC34 (p = 3.69 × 10-18 ). In the context of lithium, we confirm that chronic use in a sample of 384 bipolar disorder patients is associated with longer telomeres (p = 0.03). As complementary evidence, we studied three orthologs of telomere length regulators in a Caenorhabditis elegans model of lithium-induced extended longevity and found all transcripts to be affected post-treatment (p < 0.05). Lithium may therefore confer its anti-ageing effects by moderating the expression of genes responsible for normal telomere length regulation. This is supported by our bipolar disorder sample, which shows that polygenic risk scores explain a higher proportion of the variance in telomere length amongst chronic lifetime lithium users (variance explained = 8.9%, p = 0.01), compared to non-users (p > 0.05). Consequently, this suggests that lithium may be catalysing the activity of endogenous mechanisms that promote telomere lengthening, whereby its efficacy eventually becomes limited by each individual's inherent telomere maintenance capabilities. Our work indicates a potential use of polygenic risk scoring for the prediction of adult telomere length and consequently lithium's anti-ageing efficacy.
Full text links
Related Resources
Trending Papers
Interstitial Lung Disease: A Review.JAMA 2024 April 23
Review article: Recent advances in ascites and acute kidney injury management in cirrhosis.Alimentary Pharmacology & Therapeutics 2024 March 26
Executive Summary: State-of-the-Art Review: Unintended Consequences: Risk of Opportunistic Infections Associated with Long-term Glucocorticoid Therapies in Adults.Clinical Infectious Diseases 2024 April 11
Clinical practice guidelines on the management of status epilepticus in adults: A systematic review.Epilepsia 2024 April 13
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app