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Genetically Increased Telomere Length and Aging-related Traits in the UK Biobank.

08:00 EDT 11th October 2019 | BioPortfolio

Summary of "Genetically Increased Telomere Length and Aging-related Traits in the UK Biobank."

Telomere length (TL) shortens over time in most human cell types and is a potential biomarker of aging. However, the causal association of TL on physical and cognitive traits that decline with age has not been extensively examined in middle-aged adults. Using a Mendelian randomization (MR) approach, we utilized genetically increased TL (GI-TL) to estimate the causal association of TL on aging-related traits among UK Biobank (UKB) participants (age 40-69 years). We manually curated 53 aging-related traits from the UKB and restricted to unrelated participants of British ancestry (n=337,522). We estimated GI-TL as a linear combination of nine TL-associated SNPs, each weighted by its previously-reported association with leukocyte TL. Regression models were used to assess the associations between GI-TL and each trait. We obtained MR estimates using the two-sample inverse variance weighted (IVW) approach. We identified 6 age-related traits associated with GI-TL (Bonferroni-corrected threshold p < 0.001): pulse pressure (PP) (p=5.2x10-14), systolic blood pressure (SBP) (p=2.9x10-15), diastolic blood pressure (DBP) (p=5.5x10-6), hypertension (p=5.5x10-11), forced expiratory volume (FEV1) (p=0.0001), and forced vital capacity (FVC) (p=3.8x10-6). Under MR assumptions, one standard deviation increase in TL (~1200 base pairs) increased PP, SBP, and DBP by 1.5, 2.3, and 0.8 mmHg, respectively, while FEV1 and FVC increased by 34.7 and 52.2 mL, respectively. The observed associations appear unlikely to be due to selection bias based on analyses including inverse probability weights and analyses of simulated data. These findings suggest that longer TL increases pulmonary function and blood pressure traits among middle-aged UKB participants.

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This article was published in the following journal.

Name: The journals of gerontology. Series A, Biological sciences and medical sciences
ISSN: 1758-535X
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Medical and Biotech [MESH] Definitions

The loss of some TELOMERE sequence during DNA REPLICATION of the first several base pairs of a linear DNA molecule; or from DNA DAMAGE. Cells have various mechanisms to restore length (TELOMERE HOMEOSTASIS.) Telomere shortening is involved in the progression of CELL AGING.

Maintenance of TELOMERE length. During DNA REPLICATION, chromosome ends loose some of their telomere sequence (TELOMERE SHORTENING.) Various cellular mechanism are involved in repairing, extending, and recapping the telomere ends.

A ubiquitously expressed telomere-binding protein that is present at TELOMERES throughout the CELL CYCLE. It is a suppressor of telomere elongation and may be involved in stabilization of telomere length. It is structurally different from TELOMERIC REPEAT BINDING PROTEIN 2 in that it contains acidic N-terminal amino acid residues.

A ubiquitously expressed telomere-binding protein that is present at TELOMERES throughout the cell cycle. It is a suppressor of telomere elongation and may be involved in stabilization of telomere length. It is structurally different from TELOMERIC REPEAT BINDING PROTEIN 1 in that it contains basic N-terminal amino acid residues.

Proteins that specifically bind to TELOMERES. Proteins in this class include those that perform functions such as telomere capping, telomere maintenance and telomere stabilization.

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