Age-associated telomere shortening in Thoroughbred horses

Denham, Joshua; Stevenson, Kim; Denham, Michele M.

doi:10.1016/j.exger.2019.110718

Cited by 7 publications

(7 citation statements)

References 22 publications

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“…Five of the 11 middle-aged horses also had at least one common ancestor one or two generations prior. Considering that horses possess similar telomere lengths to that of humans [15], the lack of inbreeding in the horses used in the present study and the specific value of the animals as an athlete model, these findings may be more generalisable to humans than rodents.…”

Section: Discussionmentioning

confidence: 71%

“…To examine if the molecular mechanisms governing shelterin and TERT gene expression are affected by exercise, we used a large animal model of excellent aerobic fitness. Our previous work established that telomere length is inversely related to age in Thoroughbred horses [9] and that telomeres in these large mammals are much more similar in length to that of humans than in small animal models, such as rodents [15,20]. Unlike mice and rats, but like humans, telomerase activity is very low or absent in somatic cells from large animals.…”

Section: Introductionmentioning

confidence: 99%

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Exercise regulates shelterin genes and microRNAs implicated in ageing in Thoroughbred horses

Mandal

Denham²,

Spencer

et al. 2022

Pflugers Arch - Eur J Physiol

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Ageing causes a gradual deterioration of bodily functions and telomere degradation. Excessive telomere shortening leads to cellular senescence and decreases tissue vitality. Six proteins, called shelterin, protect telomere integrity and control telomere length through telomerase-dependent mechanisms. Exercise training appears to maintain telomeres in certain somatic cells, although the underlying molecular mechanisms are incompletely understood. Here, we examined the influence of a single bout of vigorous exercise training on leukocyte telomerase reverse transcriptase (TERT) and shelterin gene expression, and the abundance of three microRNAs (miRNAs) implicated in biological ageing (miRNA-143, -223 and -486-5p) in an elite athlete and large animal model, Thoroughbred horses. Gene and miRNA expression were analysed using primer-based and TaqMan Assay qPCR. Leukocyte TRF1, TRF2 and POT1 expression were all significantly increased whilst miR-223 and miR-486-5p were decreased immediately after vigorous exercise (all p < 0.05), and tended to return to baseline levels 24 h after training. Relative to the young horses (~ 3.9 years old), middle-aged horses (~ 14.8 years old) exhibited reduced leukocyte TERT gene expression, and increased POT1 and miR-223 abundance (all p < 0.05). These data demonstrate that genes transcribing key components of the shelterin-telomere complex are influenced by ageing and dynamically regulated by a single bout of vigorous exercise in a large, athletic mammal — Thoroughbred horses. Our findings also implicate TERT and shelterin gene transcripts as potential targets of miR-223 and miR-486-5p, which are modulated by exercise and may have a role in the telomere maintenance and genomic stability associated with long-term aerobic training.

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Section: Discussionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Exercise regulates shelterin genes and microRNAs implicated in ageing in Thoroughbred horses

Mandal

Denham²,

Spencer

et al. 2022

Pflugers Arch - Eur J Physiol

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“…Similar to humans, geriatric horses demonstrate age-associated alterations in leucocyte genomic stability; in one study, aged horses had increases in positive TUNEL cells, oxidative DNA damage, sister chromatid exchange and bleomycin-induced chromatid breaks when compared to non-aged adult horses [80]. Telomere length of leucocytes also decreases with age in horses, although the association between reduced telomere length and reductions in immune function in the elderly equine population have not been as clearly demonstrated as they have in aged people [81,82]. Mitogen-induced proliferation of PBMCs was also shown to be weakly correlated to relative telomere length, leading the authors to suggest other mechanisms likely have a role in age-related decrease in PBMC proliferation [82].…”

Section: Mechanisms Of Immunosenescencementioning

confidence: 99%

Immunosenescence and inflammaging in the aged horse

DeNotta

McFarlane

2023

Immun Ageing

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The equine population in the United States and worldwide now includes a higher percentage of geriatric horses than ever previously recorded, and as methods to treat and manage elderly equids are developed and refined, this aging population will likely continue to expand. A better understanding of how horses age and the effect of age on immunity and disease susceptibility is needed to enable targeted preventative healthcare strategies for aged horses. This review article outlines the current state of knowledge regarding the effect of aging on immunity, vaccine responsiveness, and disease risk in the horse, highlighting similarities and differences to what is observed in aged humans. Horses show similar but milder age-related alterations in immune function to those reported in people. Decreases in lymphocyte proliferation and antibody production and diminished response to vaccination have all been documented in elderly horses, however, increased risk of infectious disease is not commonly reported. Aged horses also show evidence of a proinflammatory state (inflammaging) yet appear less susceptible to the chronic diseases of people for which inflammation is a risk factor. Information is currently lacking as to why the horse does not experience the same risk of age-related disease (e.g., cancer, heart disease, neurodegeneration) as people, although a lack of negative lifestyle habits, differences in diet, exercise, genetics and physiology may all contribute to improved health outcomes in the older horse.

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“…In recent years, evolutionary, behavioral and biomedical research has revealed telomeres as powerful predictors of survival and longevity across vertebrates, especially among birds (Hares et al 2018, Wilbourn et al 2018, Whittemore et al 2019). Telomeres typically shorten with age during cellular replication (Levy et al 1992, Denham et al 2019), and this process can be accelerated during periods of growth (Reichert et al 2015, Vedder et al 2018) or stress exposure (von Zglinicki 2002, Chatelain et al 2020, but see Boonekamp et al 2017). Short telomeres are consequently believed to prompt senescence and loss of tissue function (Armanios and Blackburn 2012) but can be repaired by telomerase, the enzyme that re‐builds telomeric repeats (Blackburn et al 1989).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, early growth may be linked with telomere dynamics in potentially opposing ways. For instance, rapid cellular replication hastens telomere loss during development (Levy et al 1992, Denham et al 2019), but high levels of telomerase early in life (Haussmann et al 2007) may promote growth (Smith et al 2003, de Jesus et al 2011, 2012). Previous work shows that telomerase plays a role in energetics (e.g.…”

Section: Introductionmentioning

confidence: 99%

A putative telomerase activator has tissue‐specific effects on telomere length in a developing songbird

Wolf

Stansberry

Rosvall

2021

Journal of Avian Biology

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There is good evidence that telomeres predict variation in health and longevity, yet it is unclear whether these patterns are causally derived from telomeres per se, in part because relatively little research directly manipulates telomere length during early life, when telomere shortening is most dynamic. Here, we test how the telomerase activator TA‐65 (i.e. cycloastrogenol) affects telomere length in five tissues during the peak of growth in the wild tree swallow Tachycineta bicolor. Following eight days of oral TA‐65 administration, chicks experienced telomere lengthening in the blood and accelerated feather growth, but no changes to mass over time. TA‐65 did not affect telomere length in the brain or spleen and led to shorter telomeres in the liver and adrenals. This whole‐organism experimental manipulation of telomere dynamics therefore reveals limitations to telomere protection and biological senescence. In doing so, this work advances our understanding of early‐life telomere dynamics and their potential role in generating future variation in health and lifespan.

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Age-associated telomere shortening in Thoroughbred horses

Cited by 7 publications

References 22 publications

Exercise regulates shelterin genes and microRNAs implicated in ageing in Thoroughbred horses

Exercise regulates shelterin genes and microRNAs implicated in ageing in Thoroughbred horses

Immunosenescence and inflammaging in the aged horse

A putative telomerase activator has tissue‐specific effects on telomere length in a developing songbird

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