Early-life telomere length predicts survival to adulthood and lifespan in a wild mammal

Telomeres, protective caps at the end of chromosomes, maintain genomic stability and function as a biomarker of senescence in many vertebrate species. Telomere length at different ages has been related to (subsequent) lifespan, but to date only one laboratory-based study has shown a direct link between early-life telomere length and lifespan. Whether this relationship holds in wild populations, where individuals are subject to variable natural conditions that may mask relationships seen in controlled laboratory settings, remains unknown. Here, we provide evidence that early-life telomere length predicts survival to adulthood in a wild population of European badgers (Meles meles). Furthermore, both early-life telomere length and telomere rate of change predict lifespan. We found a complex cross-sectional relationship between telomere length and age, where telomeres shortened over the first 38 months, but with no uniform loss after this point. We found little within-individual consistency in telomere length across lifespan, where telomere length did not predict residual lifespan. Importantly, we also observed increases in mean telomere length within individuals, which could not be explained by measurement error alone. Early-life telomere length varied distinctly among cohorts, indicating a role for early-life environment and additive genetic effects. Our results elaborate on the dynamic way that telomeres function as a biomarker of senescence in a wild mammal, where telomere length and rate of change can reflect short-term and lasting effects of early-life conditions on individual life-history.

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Born to be young? Prenatal thyroid hormones increase early-life telomere length in wild collared flycatchers

Biology Letters ◽

10.1098/rsbl.2020.0364 ◽

2020 ◽

Vol 16 (11) ◽

pp. 20200364

Author(s):

Antoine Stier ◽

Bin-Yan Hsu ◽

Coline Marciau ◽

Blandine Doligez ◽

Lars Gustafsson ◽

...

Keyword(s):

Thyroid Hormones ◽

Telomere Length ◽

Early Life ◽

Copy Number ◽

Growth Period ◽

Mtdna Copy Number ◽

Cross Sectional ◽

Telomere Shortening ◽

Underlying Mechanisms ◽

Age At Birth

The underlying mechanisms of the lifelong consequences of prenatal environmental condition on health and ageing remain little understood. Thyroid hormones (THs) are important regulators of embryogenesis, transferred from the mother to the embryo. Since prenatal THs can accelerate early-life development, we hypothesized that this might occur at the expense of resource allocation in somatic maintenance processes, leading to premature ageing. Therefore, we investigated the consequences of prenatal TH supplementation on potential hallmarks of ageing in a free-living avian model in which we previously demonstrated that experimentally elevated prenatal TH exposure accelerates early-life growth. Using cross-sectional sampling, we first report that mitochondrial DNA (mtDNA) copy number and telomere length significantly decrease from early-life to late adulthood, thus suggesting that these two molecular markers could be hallmarks of ageing in our wild bird model. Elevated prenatal THs had no effect on mtDNA copy number but counterintuitively increased telomere length both soon after birth and at the end of the growth period (equivalent to offsetting ca 4 years of post-growth telomere shortening). These findings suggest that prenatal THs might have a role in setting the ‘biological' age at birth, but raise questions about the nature of the evolutionary costs of prenatal exposure to high TH levels.

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Estimation of environmental and genetic contributions to telomere length variation in a wild mammal

10.32942/osf.io/s5dnr ◽

2020 ◽

Author(s):

Sil H. J. van Lieshout ◽

Alex Sparks ◽

Amanda Bretman ◽

Chris Newman ◽

Christina D. Buesching ◽

...

Keyword(s):

Telomere Length ◽

Individual Variation ◽

Evolutionary Dynamics ◽

Meles Meles ◽

Length Variation ◽

Phenotypic Variance ◽

Parental Age ◽

Transgenerational Effects ◽

Wild Mammal ◽

Relative Contribution

Understanding individual variation in fitness-related traits requires separating the environmental and genetic determinants. Telomeres are protective caps at the ends of chromosomes that are thought to be a biomarker of senescence as their length predicts mortality risk and reflect the physiological consequences of environmental conditions. The relative contribution of genetic and environmental factors to individual variation in telomere length is however unclear, yet important for understanding its evolutionary dynamics. In particular, the evidence for transgenerational effects, in terms of parental age at conception, on telomere length is mixed. Here, we investigate the heritability of telomere length, using the ‘animal model’, and parental age at conception effects on offspring telomere length in a wild population of European badgers (Meles meles). While we found no heritability of telomere length, our power to detect heritability was low and a repeatability of 2% across individual lifetimes provides a low upper limit to ordinary heritability. However, year (25%) and cohort (3%) explained greater proportions of the phenotypic variance in telomere length. There was no support for parental age at conception effects, or for longitudinal within-parental age effects on offspring telomere length. Our results indicate a lack of transgenerational effects through parental age at conception and a low potential for evolutionary change in telomere length in this population. Instead, we provide evidence that individual variation in telomere length is largely driven by environmental variation in this wild mammal.

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Age-related declines in immune response in a wild mammal are unrelated to immune cell telomere length

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2015.2949 ◽

2016 ◽

Vol 283 (1825) ◽

pp. 20152949 ◽

Cited By ~ 13

Author(s):

Christopher Beirne ◽

Laura Waring ◽

Robbie A. McDonald ◽

Richard Delahay ◽

Andrew Young

Keyword(s):

Telomere Length ◽

Individual Variation ◽

Immune Cell ◽

Ex Vivo ◽

Natural Populations ◽

Population Level ◽

Meles Meles ◽

Wild Mammal ◽

Age Related ◽

Age Variation

Senescence has been hypothesized to arise in part from age-related declines in immune performance, but the patterns and drivers of within-individual age-related changes in immunity remain virtually unexplored in natural populations. Here, using a long-term epidemiological study of wild European badgers ( Meles meles ), we (i) present evidence of a within-individual age-related decline in the response of a key immune-signalling cytokine, interferon-gamma (IFN γ ), to ex vivo lymphocyte stimulation, and (ii) investigate three putative drivers of individual variation in the rate of this decline (sex, disease and immune cell telomere length; ICTL). That the within-individual rate of age-related decline markedly exceeded that at the population level suggests that individuals with weaker IFN γ responses are selectively lost from this population. IFN γ responses appeared to decrease with the progression of bovine tuberculosis infection (independent of age) and were weaker among males than females. However, neither sex nor disease influenced the rate of age-related decline in IFN γ response. Similarly, while ICTL also declines with age, variation in ICTL predicted neither among- nor within-individual variation in IFN γ response. Our findings provide evidence of within-individual age-related declines in immune performance in a wild mammal and highlight the likely complexity of the mechanisms that generate them.

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Birth weight influences the kidney size and function of Bangladeshi children

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174417000976 ◽

2017 ◽

Vol 9 (4) ◽

pp. 386-394 ◽

Cited By ~ 4

Author(s):

F. Ferdous ◽

E. Ma ◽

R. Raqib ◽

Y. Wagatsuma

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Early Life ◽

Kidney Volume ◽

Normal Birth Weight ◽

Kidney Size ◽

Normal Birth ◽

Life Conditions ◽

Early Life Conditions ◽

And Function

Early-life conditions influence organ growth patterns and their functions, as well as subsequent risk for non-communicable chronic diseases in later life. A limited number of studies have determined that in Bangladesh, kidney size relates to its function among children as a consequence of the maternal and postnatal conditions. The present study objectives were to determine early-life conditions in relation to childhood kidney size and to compare their influences on kidney function. The study was embedded in a population-based prospective cohort of 1067 full-term singleton live births followed from fetal life onward. Kidney volume was measured by ultrasound in children at the age of 4.5 years (range 45–64 months), and the estimated glomerular filtration rate (eGFR) was assessed at the age of 9 years (range 96–116 months). The mean (s.d.) kidney volume of children at 4.5 years was 64.2 (11.3) cm3, with a significant mean difference observed between low birth weight and normal birth weight children (P<0.001). The multivariable model showed, changes in status from low birth weight to normal birth weight children, with kidney volume increases of 2.92 cm3/m2, after adjusting for the child’s age, sex, maternal age and early pregnancy body mass index, and socio-economic index variables. One-unit change in kidney volume (cm3/m2) improved the eGFR to 0.18 ml/min/1.73 m2. The eGFR in low birth weight children was 5.44 ml/min/1.73 m2 less than that in normal birth weight children after adjustments. Low birth weight leads to adverse effects on kidney size and function in children.

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Early-life conditions impact juvenile telomere length, but do not predict later life-history strategies or fitness in a wild vertebrate

10.32942/osf.io/24rbk ◽

2021 ◽

Author(s):

Janske van de Crommenacker ◽

Martijn Hammers ◽

Hannah Louise Dugdale ◽

Terry Burke ◽

Jan Komdeur ◽

...

Keyword(s):

Life History ◽

Telomere Length ◽

Environmental Conditions ◽

Early Life ◽

Later Life ◽

Effective Measure ◽

Life Conditions ◽

The Future ◽

Early Life Conditions ◽

The Impact

1.Environmental conditions experienced during early life may have long-lasting effects on later-life phenotypes and fitness. Individuals experiencing poor early-life conditions may suffer subsequent fitness constraints. Alternatively, individuals may use a strategic ‘Predictive Adaptive Response’ (PAR), whereby they respond – in terms of physiology or life-history strategy – to the conditions experienced in early life to maximise later-life fitness. In particular, the Future Lifespan Expectation (FLE) PAR hypothesis predicts that when poor early-life conditions negatively impact an individual’s physiological state, individuals will accelerate their reproductive schedule to maximise fitness during their shorter predicted lifespan.2.We aimed to measure the impact of early-life conditions and resulting fitness across individual lifetimes to test the predictions of the FLE hypothesis in a wild, long-lived model species. 3.Using a long-term individual-based dataset, we investigated how early-life conditions are linked with subsequent fitness in an isolated population of the Seychelles warbler (Acrocephalus sechellensis). How individuals experience early-life environmental conditions may vary greatly, so we also tested whether telomere length – shorter telomers are a biomarker of an individual’s exposure to stress – can provide an effective measure of the individual-specific impact of early-life conditions. Specifically, under the FLE hypothesis, we would expect shorter telomeres to be associated with accelerated reproduction. 4.Contrary to expectations, shorter juvenile telomere length was not associated with poor early-life conditions, but instead with better conditions, probably as a result of faster juvenile growth. Furthermore, neither juvenile telomere length, nor other measures of early-life conditions, were associated with age of first reproduction or the rate of early-life reproduction in either sex. These results do not support the key prediction of the Future Lifetime Expectation PAR hypothesis. 5.We found no support for the FLE hypothesis. However, at least for males, poor early-life body conditions were associated with lower first year survival and reduced longevity, indicating that poor early-life conditions pose subsequent fitness constraints. Our results also showed that using juvenile telomere length as a measure of early-life conditions requires caution, as it is likely to not only reflect environmental stress but also other processes such as growth.

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Associations between DNA methylation and telomere length during early life: insight from wild zebra finches (Taeniopygia guttata)

10.22541/au.161715129.96880077/v1 ◽

2021 ◽

Author(s):

Elizabeth Sheldon ◽

Riccardo Ton ◽

Winnie Boner ◽

Pat Monaghan ◽

Shirley Raveh ◽

...

Keyword(s):

Dna Methylation ◽

Growth Rate ◽

Telomere Length ◽

Early Life ◽

Life History Traits ◽

Zebra Finches ◽

Ecological Context ◽

Life Conditions ◽

Early Life Conditions ◽

Length Changes

Telomere length and DNA methylation (DNAm) are two promising biomarkers of biological age. Environmental factors and life history traits are known to affect variation in both these biomarkers, especially during early life, yet surprisingly little is known about their reciprocal association. Here, we present the first study on a natural population to explore how variation in DNAm, growth rate and early-life conditions are associated with telomere length changes during development. We tested these associations by collecting data from wild, nestling zebra finches in the Australian desert. We found that increases in the level of DNAm were negatively correlated with telomere length changes across early life. We also confirm previously documented effects of post hatch growth rate and clutch size on telomere length in a natural ecological context for a species that has been extensively studied in the laboratory. However, we did not detect any effect of ambient temperature during developmental on telomere dynamics. We also found that the absolute telomere length of wild zebra finches, measured using the in-gel TRF method, was similar to that of captive birds. Our findings highlight exciting new opportunities to link and disentangle potential relationships between environmental, epigenetic and telomere length dynamics during early life.

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Consequences of measurement error in qPCR telomere data: A simulation study

10.1101/491944 ◽

2018 ◽

Cited By ~ 1

Author(s):

Daniel Nettle ◽

Luise Seeker ◽

Dan Nussey ◽

Hannah Froy ◽

Melissa Bateson

Keyword(s):

Measurement Error ◽

Longitudinal Data ◽

Telomere Length ◽

Rate Of Change ◽

Control Gene ◽

Linear Transformations ◽

Cross Sectional ◽

Relative Telomere Length ◽

Telomere Sequence ◽

Ratio Change

AbstractThe qPCR method provides an inexpensive, rapid method for estimating relative average telomere length across a set of biological samples. Like all laboratory methods, it involves some degree of measurement error. The estimation of relative telomere length is done subjecting the actual measurements made (the Cq values for telomere and a control gene) to non-linear transformations and combining them into a ratio. Here, we use computer simulations, supported by mathematical analysis, to explore how errors in measurement affect qPCR estimates of relative telomere length, both in cross-sectional and longitudinal data. We show that errors introduced at the level of Cq values are magnified when the TS ratio is calculated. If the errors at the Cq level are normally distributed and independent of telomere length, those in the TS ratio are positively skewed and proportional to telomere length. The repeatability of the TS ratio declines abruptly with increasing error in measurement of the telomere sequence and/or the control gene. In simulated longitudinal data, measurement error alone can produce a pattern of low correlation between successive measures of telomere length, coupled with a strong dependency of the rate of change on initial telomere length. Our results illustrate the importance of control of measurement error: a small increase in error in Cq values can have large consequences for the power and interpretability of qPCR estimates of relative telomere length. They also illustrate the importance of characterising the measurement error that exists in each dataset—coefficients of variation are generally unhelpful, and researchers should report standard deviations of Cq values and/or repeatabilities of TS ratios—and allowing for the known effects of measurement error when interpreting patterns of TS ratio change over time.

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