Metabolomics profiling reveals novel markers for leukocyte telomere length
Jonas ZiererGabi KastenmüllerKarsten SuhreChristian GiegerVeryan CoddPei-Chien TsaiJordana T. BellAnnette PetersKonstantin StrauchHolger SchulzStephan WeidingerRobert P. MohneyNilesh J. SamaniTim D. SpectorMassimo ManginoCristina Menni
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Abstract:
Aging | doi:10.18632/aging.100874. Jonas Zierer, Gabi Kastenmüller, Karsten Suhre, Christian Gieger, Veryan Codd, Pei-Chien Tsai, Jordana Bell, Annette Peters, Konstantin Strauch, Holger Schulz, Stephan Weidinger, Robert P. Mohney, Nilesh J. Samani, Tim Spector, Massimo Mangino, Cristina MenniKeywords:
Profiling (computer programming)
Constitutive heterochromatin
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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.
Songbird
Senescence
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Senescence
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Telomere length and telomere shortening predict survival in many organisms. This raises the question of the contribution of genetic and environmental effects to variation in these traits, which is still poorly known, particularly for telomere shortening. We used experimental (cross-fostering) and statistical (quantitative genetic "animal models") means to disentangle and estimate genetic and environmental contributions to telomere length variation in pedigreed free-living jackdaws (Corvus monedula). Telomere length was measured twice in nestlings, at ages 4 (n = 715) and 29 days (n = 474), using telomere restriction fragment (TRF) analysis, adapted to exclude interstitial telomeric sequences. Telomere length shortened significantly over the nestling period (10.4 ± 0.3 bp day-1 ) and was highly phenotypically (rP = 0.95 ± 0.01) and genetically (rG > 0.99 ± 0.01) correlated within individuals. Additive genetic effects explained a major part of telomere length variation among individuals, with its heritability estimated at h2 = 0.74 on average. We note that TRF-based studies reported higher heritabilities than qPCR-based studies, and we discuss possible explanations. Parent-offspring regressions yielded similar heritability estimates for mothers and fathers when accounting for changes in paternal telomere length over life. Year effects explained a small but significant part of telomere length variation. Heritable variation for telomere shortening was low (h2 = 0.09 ± 0.11). The difference in heritability between telomere length (high) and telomere shortening (low) agrees with evolutionary theory, in that telomere shortening has stronger fitness consequences in this population. Despite the high heritability of telomere length, its evolvability, which scales the additive genetic variance by mean telomere length, was on average 0.48%. Hence, evolutionary change of telomere length due to selection is likely to be slow.
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Subtelomere
Antigenic variation
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Telomerase RNA component
Telomere-binding protein
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