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Leukocyte Telomere Length Linked to Age, Sex, Ancestry in UK Biobank Analysis

NEW YORK — The length of telomeres in leukocytes varies with age, sex, and ancestry, among other factors, a new analysis of UK Biobank samples has found.

As telomeres shorten with each cell division, their length reflects cellular age and may also be a biomarker of biological age. Using data on telomere length measured in leukocytes from UK Biobank participants, researchers from the University of Leicester and elsewhere generated a resource of leukocyte telomere length, or LTL, as they reported in the journal Nature Aging on Thursday.

Using that data, they confirmed previous studies showing that older age or being male is associated with shorter telomeres. They further noted links between ethnic ancestries and paternal age at birth and leukocyte telomere length, and they determined the within-individual variance in telomere length over five years.

"[W]e have created a large resource to facilitate investigation of the determinants and biomedical consequences of interindividual variation in LTL," Leicester's Nilesh Samani and colleagues wrote in their paper, adding that the "[d]emonstration of several well-established relationships of LTL should give researchers additional confidence in the use of the resource."

The researchers obtained LTL measurements for 474,074 individuals from the UK Biobank. But because they performed the measurements over the course of four years and used different reagents and equipment, they searched and adjusted for possible sources of technical noise, such as the PCR machine used or the operator. After accounting for these variables, the LTL measurements were more consistent, and a set of blinded duplicates had high reproducibility.

The researchers then examined the relationship between LTL and a number of phenotypes like age and sex, where LTL is thought to vary, as well as with ethnicity and paternal age, where the connections have been more tenuous. Through this, they confirmed the relationship between shorter LTLs and older age as well as being male.

Being female was, in terms of telomere length, the equivalent to being 7.4 years younger in biological age, which the researchers noted is similar to a previous estimate of 7 years. However, they also found that the effect was more pronounced among younger women than older, postmenopausal women, suggesting that estrogen could have an effect on LTL. The study was limited by the narrow age range of UK Biobank participants, who are between 40 and 70 years old.

Additionally, compared to white Europeans, individuals of Black, Chinese, and mixed ancestries had longer LTLs. Within each ethnic group, the researchers noted similar relationships between age, sex, and LTL.

For a subset of UKB individuals, the researchers had data on paternal and maternal age. After adjusting for age and sex, they found that having an older mother or father at birth was associated with longer LTL. However, further analysis indicated that the effect was largely driven by paternal age.

Overall, these factors explain about 5.5 percent of the variance in LTL, with age accounting for the largest portion of that, about 3.5 percent of the variance. They further noted that, based on samples taken five years apart, LTL varies within individuals over time, similar to variations observed in blood pressure or cholesterol.

"Our analyses highlight the scope and potential of this powerful and detailed resource, which is available to the worldwide research community through application to UKB," the researchers added.