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Invited Commentary: “Is physical fitness associated with leukocyte telomere length in youth with type 1 diabetes?”

Pediatric Research volume 97, pages 2196–2197 (2025)Cite this article

Telomeres in humans are tandem highly conserved nucleotide sequence repeats, part of a ribonucleoprotein structure, at the end of linear chromosomes, that protect chromosome ends and gradually erode with each cell division, due to the end replication problem.1 The hexameric (50-TTAGGG-30) repeats cap shields the chromosome from degradation and prevents recognition as a site of DNA double strand break.2 The preservation of telomere length or the dysfunction of end-capping has been previously associated with genomic instability and the progressive shortening of telomeres with aging.2 In humans, telomere length can range from 3 to 20 kilobase pairs showcasing significant variability in both adults and children, while within the individual following each cell division, telomere length shortens progressively.3 This happens because the ends of linear DNA cannot be replicated completely during lagging strand DNA synthesis.3 Physiologically cells maintain telomere length with telomerase, a ribonucleoprotein enzyme complex that consists of telomeric reverse transcriptase, and telomeric RNA component and which synthesizes telomeric DNA at the end of linear chromosomes.2 In the human fetus, telomerase is constitutively active in all body cells, however, after birth, it remains predominantly active in germline cells, activated lymphocytes, and specific stem cell populations, while most somatic tissues exhibit no telomerase activity.3 Cancer cells restore telomere length through two potential mechanisms: the activation of telomerase (commonly expressed in neoplastic cells), or through alternative lengthening of telomeres via recombination (continuous proliferation of cells in the absence of telomerase activity).2 In addition, oxidative stress (the pro-oxidation component) is associated with telomere shortening and dysfunction.2 Conversely, antioxidant defenses have been shown to be important in maintaining telomere integrity, potentially reducing progression of vascular ageing in type 2 diabetes patients.4

Various factors may influence telomeric dynamics over time.1 Relevant research has tried to show the relative effect of pubertal development, sex or genetic background on increased telomere length in young people.1 It should be noted, that specific conditions can expedite telomere length attrition even in children through oxidative, immune, hormonal, and metabolic pathways, pathophysiological mechanisms associated with the development or the increased susceptibility to disease.5 Previous research has shown shorter telomere length in individuals with diabetes as opposed to healthy individuals.6,7 Evidence suggest that telomere length in type 1 diabetes is inversely related to disease duration, and weakly correlates with pulse pressure and vascular risk factors.7 In addition, telomere length has been associated with the progression of diabetic nephropathy.8 Of note, previous studies suggest that good glycemic control in type 1 diabetes can attenuate, though not completely prevent, telomere shortening in mononuclear cells.9

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  1. Division of Diabetes and Metabolism, 2nd Department of Pediatrics of the National and Kapodistrian University of Athens, “P. & A. Kyriakou” Children’s Hospital, Athens, Greece

    George Paltoglou

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  1. George Paltoglou
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Correspondence to George Paltoglou.

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Paltoglou, G. Invited Commentary: “Is physical fitness associated with leukocyte telomere length in youth with type 1 diabetes?”. Pediatr Res 97, 2196–2197 (2025). https://doi.org/10.1038/s41390-025-03988-0

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