Telomere length and dynamics predict mortality in a wild longitudinal study

Explaining variation in life expectancy between individuals of the same age is fundamental to our understanding of population ecology and life history evolution. Variation in the length and rate of loss of the protective telomere chromosome caps has been linked to cellular lifespan. Yet, the extent to which telomere length and dynamics predict organismal lifespan in nature is still contentious. Using longitudinal samples taken from a closed population of Acrocephalus sechellensis (Seychelles warblers) studied for over 20 years, we describe the first study into life‐long adult telomere dynamics (1–17 years) and their relationship to mortality under natural conditions (n = 204 individuals). We show that telomeres shorten with increasing age and body mass, and that shorter telomeres and greater rates of telomere shortening predicted future mortality. Our results provide the first clear and unambiguous evidence of a relationship between telomere length and mortality in the wild, and substantiate the prediction that telomere length and shortening rate can act as an indicator of biological age further to chronological age when exploring life history questions in natural conditions.     

Telomere length is reflected by plumage coloration and predicts seasonal reproductive success in the barn swallow

Individuals differ in realized fitness but the genetic/phenotypic traits that underpin such variation are often unknown. Telomere dynamics may be a major source of variation in fitness traits because physiological telomere shortening depends on environmental and genetic factors and may impair individual performance. Here, we showed that, in a population of a socially monogamous, biparental passerine bird, the barn swallow (Hirundo rustica), breeding in northern Italy, telomere length (TL) of both adult males and females positively correlated with seasonal reproductive and fledging success, as expected because long telomeres are supposed to boost performance. Telomere length was correlated with sexually dimorphic coloration in both sexes, showing for the first time in any species that coloration reliably reflects TL and may mediate mutual mate choice, leading to the observed positive assortative mating for TL in the barn swallow. Thus, TL appears to be associated with variation in a major fitness trait and may be an ultimate target of mate choice, as individuals of both sexes can use coloration to adaptively choose high‐quality mates that possess long telomeres.     

The association between stressors and telomeres in non‐human vertebrates: a meta‐analysis

Animal response to stressors such as harsh environmental conditions and demanding biological processes requires energy generated through increased mitochondrial activity. This results in the production of reactive oxygen species (ROS). In vitro and some in vivo studies suggest that oxidative damage of DNA caused by ROS is responsible for telomere shortening. Since telomere length is correlated with survival in many vertebrates, telomere loss is hypothesised to trigger cellular ageing and/ or to reflect the harshness of the environment an individual has experienced. To improve our understanding of stress‐induced telomere dynamics in non‐human vertebrates, we analysed 109 relevant studies in a meta‐analytical framework. Overall, the exposure to possible stressors was associated with shorter telomeres or higher telomere shortening rate (average effect size = ?0.16 ± 0.03). This relationship was consistent for all phylogenetic classes and for all a priori‐selected stressor categories. It was stronger in the case of pathogen infection, competition, reproductive effort and high activity level, which emphasises their importance in explaining intraspecific telomere length variability and, potentially, lifespan variability. Interestingly, the association between stressor exposure and telomeres in one hand, and oxidative stress in the other hand, covaried, suggesting the implication of oxidative stress in telomere dynamics.     

Telomeres, age and reproduction in a long-lived reptile

A major interest has recently emerged in understanding how telomere shortening, mechanism triggering cell senescence, is linked to organism ageing and life history traits in wild species. However, the links between telomere length and key history traits such as reproductive performances have received little attention and remain unclear to date. The leatherback turtle Dermochelys coriacea is a long-lived species showing rapid growth at early stages of life, one of the highest reproductive outputs observed in vertebrates and a dichotomised reproductive pattern related to migrations lasting 2 or 3 years, supposedly associated with different environmental conditions. Here we tested the prediction of blood telomere shortening with age in this species and investigated the relationship between blood telomere length and reproductive performances in leatherback turtles nesting in French Guiana. We found that blood telomere length did not differ between hatchlings and adults. The absence of blood telomere shortening with age may be related to an early high telomerase activity. This telomere-restoring enzyme was formerly suggested to be involved in preventing early telomere attrition in early fast-growing and long-lived species, including squamate reptiles. We found that within one nesting cycle, adult females having performed shorter migrations prior to the considered nesting season had shorter blood telomeres and lower reproductive output. We propose that shorter blood telomeres may result from higher oxidative stress in individuals breeding more frequently (i.e., higher costs of reproduction) and/or restoring more quickly their body reserves in cooler feeding areas during preceding migration (i.e., higher foraging costs). This first study on telomeres in the giant leatherback turtle suggests that blood telomere length predicts not only survival chances, but also reproductive performances. Telomeres may therefore be a promising new tool to evaluate individual reproductive quality which could be useful in such species of conservation concern.     

Sex differences in telomeres and lifespan in Soay sheep: From the beginning to the end

There is tremendous diversity in ageing rates and lifespan not only among taxa but within species, and particularly between the sexes. Women often live longer than men, and considerable research on this topic has revealed some of the potential biological, psychological and cultural causes of sex differences in human ageing and lifespan. However, sex differences in lifespan are widespread in nonhuman animals suggesting biology plays a prominent role in variation in ageing and lifespan. Recently, evolutionary biologists have borrowed techniques from biomedicine to identify whether similar mechanisms causing or contributing to variation in ageing and lifespan in humans and laboratory animals also operate in wild animals. Telomeres are repetitive noncoding DNA sequences capping the ends of chromosomes that are important for chromosomal stability but that can shorten during normal cell division and exposure to stress. Telomere shortening is hypothesized to directly contribute to the ageing process as once telomeres shorten to some length, the cells stop dividing and die. Men tend to have shorter telomeres and faster rates of telomere attrition with age than women, suggesting one possible biological cause of sex differences in lifespan. In this issue of Molecular Ecology, Watson et al. ( 2017 ) show that telomere lengths in wild Soay sheep are similar between females and males near the beginning of life but quickly diverge with age because males but not females showed reduced telomere lengths at older ages. The authors further show that some of the observed sex difference in telomere lengths in old age may be due to male investment in horn growth earlier in life, suggesting that sexually dimorphic allocation to traits involved in sexual selection might underlie sex differences in telomere attrition. This study provides a rare example of how biological mechanisms potentially contributing to sex differences in lifespan in humans may also operate in free‐living animals. However, future studies using a longitudinal approach are necessary to confirm these observations and identify the ultimate and proximate causes of any sex differences in telomere lengths. Collaborations between evolutionary biologists and gerontologists are especially needed to identify whether telomere lengths have a causal role in ageing, particularly in natural conditions, and whether this directly contributes to sex differences in lifespan.     

Drivers of longitudinal telomere dynamics in a long‐lived bat species,Myotis myotis

Age‐related telomere shortening is considered a hallmark of the ageing process. However, a recent cross‐sectional ageing study of relative telomere length (rTL) in bats failed to detect a relationship between rTL and age in the long‐lived genus Myotis (M. myotis and M. bechsteinii), suggesting some other factors are responsible for driving telomere dynamics in these species. Here, we test if longitudinal rTL data show signatures of age‐associated telomere attrition in M. myotis and differentiate which intrinsic or extrinsic factors are likely to drive telomere length dynamics. Using quantitative polymerase chain reaction, rTL was measured in 504 samples from a marked population, from Brittany, France, captured between 2013 and 2016. These represent 174 individuals with an age range of 0 to 7+ years. We find no significant relationship between rTL and age (p = .762), but demonstrate that within‐individual rTL is highly variable from year to year. To investigate the heritability of rTL, a population pedigree (n = 1744) was constructed from genotype data generated from a 16‐microsatellite multiplex, designed from an initial, low‐coverage, Illumina genome for M. myotis. Heritability was estimated in a Bayesian, mixed model framework, and showed that little of the observed variance in rTL is heritable (h² = 0.01–0.06). Rather, correlations of first differences, correlating yearly changes in telomere length and weather variables, demonstrate that, during the spring transition, average temperature, minimum temperature, rainfall and windspeed correlate with changes in longitudinal telomere dynamics. As such, rTL may represent a useful biomarker to quantify the physiological impact of various environmental stressors in bats.     

Disposable Soma Theory and the Evolution of Maternal Effects on Ageing

Maternal effects are ubiquitous in nature and affect a wide range of offspring phenotypes. Recent research suggests that maternal effects also contribute to ageing, but the theoretical basis for these observations is poorly understood. Here we develop a simple model to derive expectations for (i) if maternal effects on ageing evolve; (ii) the strength of maternal effects on ageing relative to direct environmental effects; and (iii) the predicted relationships between environmental quality, maternal age and offspring lifespan. Our model is based on the disposable soma theory of ageing, and the key assumption is thus that mothers trade off their own somatic maintenance against investment in offspring. This trade-off affects the biological age of offspring at birth in terms of accumulated damage, as indicated by biomarkers such as oxidative stress or telomere length. We find that the optimal allocation between investment in maternal somatic investment and investment in offspring results in old mothers and mothers with low resource availability producing offspring with reduced life span. Furthermore, the effects are interactive, such that the strongest maternal age effects on offspring lifespan are found under low resource availability. These findings are broadly consistent with results from laboratory studies investigating the onset and rate of ageing and field studies examining maternal effects on ageing in the wild.     

Telomere regulation: lessons learnt from mice and men,potential opportunities in horses

Telomeres are genetically conserved nucleoprotein complexes located at the ends of chromosomes that preserve genomic stability. In large mammals, somatic cell telomeres shorten with age, owing to the end replication problem and lack of telomere-lengthening events (e.g. telomerase and ALT activity). Therefore, telomere length reflects cellular replicative reserve and mitotic potential. Environmental insults can accelerate telomere attrition in response to cell division and DNA damage. As such, telomere shortening is considered one of the major hallmarks of ageing. Much effort has been dedicated to understanding the environmental perturbations that accelerate telomere attrition and therapeutic strategies to preserve or extend telomeres. As telomere dynamics seem to reflect cumulative cellular stress, telomere length could serve as a biomarker of animal welfare. The assessment of telomere dynamics (i.e. rate of shortening) in conjunction with telomere-regulating genes and telomerase activity in racehorses could monitor long-term animal health, yet it could also provide some unique opportunities to address particular limitations with the use of other animal models in telomere research. Considering the ongoing efforts to optimise the health and welfare of equine athletes, the purpose of this review is to discuss the potential utility of assessing telomere length in Thoroughbred racehorses. A brief review of telomere biology in large and small mammals will be provided, followed by discussion on the biological implications of telomere length and environmental (e.g. lifestyle) factors that accelerate or attenuate telomere attrition. Finally, the utility of quantifying telomere dynamics in horses will be offered with directions for future research.     

Sex differences in sand lizard telomere inheritance: paternal epigenetic effects increases telomere heritability and offspring survival

Background

To date, the only estimate of the heritability of telomere length in wild populations comes from humans. Thus, there is a need for analysis of natural populations with respect to how telomeres evolve.

Methodology/Principal Findings

Here, we show that telomere length is heritable in free-ranging sand lizards, Lacerta agilis. More importantly, heritability estimates analysed within, and contrasted between, the sexes are markedly different; son-sire heritability is much higher relative to daughter-dam heritability. We assess the effect of paternal age on Telomere Length (TL) and show that in this species, paternal age at conception is the best predictor of TL in sons. Neither paternal age per se at blood sampling for telomere screening, nor corresponding age in sons impact TL in sons. Processes maintaining telomere length are also associated with negative fitness effects, most notably by increasing the risk of cancer and show variation across different categories of individuals (e.g. males vs. females). We therefore tested whether TL influences offspring survival in their first year of life. Indeed such effects were present and independent of sex-biased offspring mortality and offspring malformations.

Conclusions/Significance

TL show differences in sex-specific heritability with implications for differences between the sexes with respect to ongoing telomere selection. Paternal age influences the length of telomeres in sons and longer telomeres enhance offspring survival.     

Can telomere shortening explain sigmoidal growth curves?

A general branching process model is proposed to describe the shortening of telomeres in eukaryotic chromosomes. The model is flexible and incorporates many special cases to be found in the literature. In particular, we show how telomere shortening can give rise to sigmoidal growth curves, an idea first expressed by Portugal et al. [A computational model for telomere-dependent cell-replicative aging, BioSystems 91 (2008), pp. 262–267]. We also demonstrate how other types of growth curves arise if telomere shortening is mitigated by other cellular processes. We compare our results with published data sets from the biological literature.     

A model of canine leukocyte telomere dynamics

Recent studies have found associations of leukocyte telomere length (TL) with diseases of aging and with longevity. However, it is unknown whether birth leukocyte TL or its age-dependent attrition--the two factors that determine leukocyte TL dynamics--explains these associations because acquiring this information entails monitoring individuals over their entire life course. We tested in dogs a model of leukocyte TL dynamics, based on the following premises: (i) TL is synchronized among somatic tissues; (ii) TL in skeletal muscle, which is largely postmitotic, is a measure of TL in early development; and (iii) the difference between TL in leukocytes and muscle (ΔLMTL) is the extent of leukocyte TL shortening since early development. Using this model, we observed in 83 dogs (ages, 4-42 months) no significant change with age in TLs of skeletal muscle and a shorter TL in leukocytes than in skeletal muscle (P<0.0001). Age explained 43% of the variation in ΔLMTL (P<0.00001), but only 6% of the variation in leukocyte TL (P=0.035) among dogs. Accordingly, muscle TL and ΔLMTL provide the two essential factors of leukocyte TL dynamics in the individual dog. When applied to humans, the partition of the contribution of leukocyte TL during early development vs. telomere shortening afterward might provide information about whether the individual's longevity is calibrated to either one or both factors that define leukocyte TL dynamics.     

The environmental and genetic determinants of chick telomere length in Tree Swallows (Tachycineta bicolor)

Conditions during early life can have dramatic effects on adult characteristics and fitness. However, we still know little about the mechanisms that mediate these relationships. Telomere shortening is one possibility. Telomeres are long sequences of DNA that protect the ends of chromosomes. They shorten naturally throughout an individual's life, and individuals with short telomeres tend to have poorer health and reduced survival. Given this connection between telomere length (TL) and fitness, natural selection should favor individuals that are able to retain longer telomeres for a greater portion of their lives. However, the ability of natural selection to act on TL depends on the extent to which genetic and environmental factors influence TL. In this study, we experimentally enlarged broods of Tree Swallows (Tachycineta bicolor) to test the effects of demanding early‐life conditions on TL, while simultaneously cross‐fostering chicks to estimate heritable genetic influences on TL. In addition, we estimated the effects of parental age and chick sex on chick TL. We found that TL is highly heritable in Tree Swallow chicks, and that the maternal genetic basis for TL is stronger than is the paternal genetic basis. In contrast, the experimental manipulation of brood size had only a weak effect on chick TL, suggesting that the role of environmental factors in influencing TL early in life is limited. There was no effect of chick sex or parental age on chick TL. While these results are consistent with those reported in some studies, they are in conflict with others. These disparate conclusions might be attributable to the inherent complexity of telomere dynamics playing out differently in different populations or to study‐specific variation in the age at which subjects were measured.     

Age Dynamics of Telomere Length in Endemic Baikal Planarians

Molecular Biology - Age-related changes in telomere length (TL) in somatic tissues are not limited only to shortening. It is known that many organisms show different TL dynamics. Such species...     

Lower red blood cell counts in middle-aged subjects with shorter peripheral blood leukocyte telomere length

Although telomere biology was revealed to play an important role in several hematopoietic disorders, its impact on the age-dependent dynamics of regular hematopoiesis is poorly understood. In vitro results suggest that particularly the erythropoietic capacity might be limited by critically short telomere length (TL). However, it remains unclear whether TL also affects erythropoiesis in healthy individuals in vivo. Therefore, we analyzed the associations between relevant hematopoietic parameters and peripheral blood leukocyte TL in the apparently healthy Asklepios study population, aged approximately 35-55 years (N > 2500). Our data indicate a clear positive, age and paternal age at birth adjusted, correlation between TL and red blood cell count, both in men (p < 0.001) and women (p = 0.011). This association was particularly significant in the older segment of the population (> 45 years old, both sexes: p = 0.003) and in younger men (p = 0.013), but not in younger women (p = 0.521). Further adjustment for known determinants in a general linear model revealed that peripheral blood leukocyte TL is most probably an independent predictor of red blood cell count (p < 0.001), suggesting that critical telomere shortening might also limit erythropoiesis in vivo. While negligible in a middle-aged population, the clinical consequences might be important in the elderly (e.g. in anemia of chronic disease). Further studies are required to confirm the impact of our results.     

Pre-diagnostic telomere length and colorectal cancer risk

BackgroundProgressive telomere shortening may be related to genomic instability and carcinogenesis. Prospective evidence relating telomere length (TL) with colorectal cancer (CRC) risk has been limited and inconsistent.MethodsWe examined the association between pre-diagnostic peripheral blood leukocyte TL and CRC risk in two matched case-control studies nested within the Nurses’ Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). Relative leukocyte TL was measured using qPCR among 356 incident CRC cases and 801 controls (NHS: 186/465, HPFS: 170/336).ResultsWe did not find a significant association between pre-diagnostic TL and CRC risk [in all participants, multivariable-adjusted odds ratio (OR) (95% CI) for TL Quartile 1 (shortest) vs. Quartile 4 (longest) = 1.36 (0.85, 2.17), P-trend = 0.27; OR (95% CI) per 1 SD decrease in TL = 1.12 (0.92, 1.36)].ConclusionsOur prospective analysis did not support a significant association between pre-diagnostic leukocyte TL and CRC risk.     

Endotoxemia,vitamin D and premature biological ageing in Arab adults with different metabolic states

There are limited studies on the association of endotoxin, a potent mediator of gut-derived inflammation and telomere length (TL). We investigated (1) the influence of adiposity on endotoxin and TL amongst Saudi adults according to type 2 diabetes mellitus (T2DM) status and (2) the influence vitamin D may have on TL attrition. Anthropometric data and fasting blood samples were taken from 775 Saudi adults visiting different primary care centers in Riyadh [387 T2DM and 388 non-T2DM]. TL, derived from peripheral blood mononuclear cells, was analyzed by Quantitative real-time polymerase chain reaction and circulating endotoxin levels by Limulus Amebocyte Lysate assay. Subjects were stratified based on obesity and T2DM status. A significant lower TL was observed in the non-obese T2DM group as compared with their non-obese, non-T2DM counterparts (p = 0.002). Significant inverse associations between TL, endotoxin and endotoxin activity were observed in the cohort with obesity. Regression analysis showed that endotoxin was a significant predictor for TL in all subjects and even after stratification according to subgroups; with variances perceived in circulating TL stronger among non-T2DM obese (10%; p = 0.003) than non-T2DM non-obese (12%; p = 0.007). Also, in the non-T2DM group, TL and HDL-cholesterol predicted 29% of the variances perceived in 25(OH)D (p < 0.001). Taken together these findings show that circulating endotoxin and 25(OH)D are associated with premature biological ageing influenced by adiposity and metabolic state; suggesting future intervention studies to manipulate gut microbiome and or vitamin D levels may offer ways to mitigate premature TL attrition.     

Can telomere shortening explain sigmoidal growth curves?

A general branching process model is proposed to describe the shortening of telomeres in eukaryotic chromosomes. The model is flexible and incorporates many special cases to be found in the literature. In particular, we show how telomere shortening can give rise to sigmoidal growth curves, an idea first expressed by Portugal et al. [A computational model for telomere-dependent cell-replicative aging, BioSystems 91 (2008), pp. 262-267]. We also demonstrate how other types of growth curves arise if telomere shortening is mitigated by other cellular processes. We compare our results with published data sets from the biological literature.     

Nestling telomere length does not predict longevity,but covaries with adult body size in wild barn swallows

Telomere length and dynamics are increasingly scrutinized as ultimate determinants of performance, including age-dependent mortality and fecundity. Few studies have investigated longevity in relation to telomere length (TL) in the wild and none has analysed longevity in relation to TL soon after hatching, despite the fact that telomere shortening may mostly occur early in life. We show that TL in nestling barn swallows (Hirundo rustica) in the wild does not predict longevity. However, TL positively covaries with body size, suggesting that individuals with large TL can afford to grow larger without paying the cost of reduced TL, and/or that benign rearing conditions ensure both large body size and low rates of telomere shortening. Overall, our study hints at a role of TL in developmental processes, but also indicates a need for further analyses to assess the expectation that TL in young individuals predicts longevity in the wild.     

Early‐breeding females experience greater telomere loss

Annual reproductive success is often highest in individuals that initiate breeding early, yet relatively few individuals start breeding during this apparently optimal time. This suggests that individuals, particularly females who ultimately dictate when offspring are born, incur costs by initiating reproduction early in the season. We hypothesized that increases in the ageing rate of somatic cells may be one such cost. Telomeres, the repetitive DNA sequences on the ends of chromosomes, may be good proxies of biological wear and tear as they shorten with age and in response to stress. Using historical data from a long‐term study population of dark‐eyed juncos (Junco hyemalis), we found that telomere loss between years was greater in earlier breeding females, regardless of chronological age. There was no relationship between telomere loss and the annual number of eggs laid or chicks that reached independence. However, telomere loss was greater when temperatures were cooler, and cooler temperatures generally occur early in the season. This suggests that environmental conditions could be the primary cause of accelerated telomere loss in early breeders.     

Age-independent telomere length predicts fitness in two bird species

Telomeres are dynamic DNA-protein structures that form protective caps at the ends of eukaryotic chromosomes. Although initial telomere length is partly genetically determined, subsequent accelerated telomere shortening has been linked to elevated levels of oxidative stress. Recent studies show that short telomere length alone is insufficient to induce cellular senescence; advanced attrition of these repetitive DNA sequences does, however, reflect ageing processes. Furthermore, telomeres vary widely in length between individuals of the same age, suggesting that individuals differ in their exposure or response to telomere-shortening stress factors. Here, we show that residual telomere length predicts fitness components in two phylogenetically distant bird species: longevity in sand martins, Riparia riparia, and lifetime reproductive success in dunlins, Calidris alpina. Our results therefore imply that individuals with longer than expected telomeres for their age are of higher quality.