Understanding determinants of individual variation in senescence in a natural population

Lead Research Organisation: University of Leeds
Department Name: Sch of Biology

Abstract

As individuals reach older ages their bodies deteriorate - at the cellular to whole body level - a process known as senescence. It is clear that individuals differ greatly in the age at which they start to senesce, and how quickly they then deteriorate. For example, a study of 38-year-old humans reported biological ages (i.e. a measure of the intrinsic condition / health of the individual rather than how long they have been alive) that varied from 28 to 61 years. However, why individuals senesce so differently remains unresolved. Indeed, this is one of the biggest unanswered questions in evolutionary biology. This has massive ramifications for health and (our ageing) society, as individuals/populations could reduce exposure to factors that negatively impact senescence so that individuals can live longer healthier lives, not to mention associated implications for animal breeding and conservation (see academic beneficiaries section).

Understanding individual variation in senescence has been hampered by a focus on a limited number of characteristics, insufficient appropriate data to measure the genetic component of senescence, and a paucity of integrated studies in natural populations where environmental factors vary and natural and sexual selection act out. These points are important. Different characteristics (e.g. reproductive ability, immunological defences, physical condition) may senesce differently, and variation in the genetic makeup of individuals may underpin different individual responses. The age of an individual's parents when it was born may also impact upon individual senescence, or reproduction early in life may affect ability to reproduce later in life. Crucially, in natural populations, environmental and social effects will combine to determine the stresses that individuals suffer, influence the expression of genetic variation, and ultimately impact on individual deterioration. Before we can mitigate the effect of deleterious factors we need to understand the relative contribution of these factors on senescence.

We aim to help remedy these shortcomings by investigating the interacting environmental, social, (non-genetic) transgenerational and genetic determinants of individual patterns of senescence in a natural population. We can only now do this because we have a unique long-term data resource from a detailed study of a population of cooperatively breeding Seychelles warblers, Acrocephalus sechellensis. Crucially, this is an isolated island population, which has allowed us to follow all individuals (over many generations) throughout their lives, collect blood samples (thus allowing individual genetic characteristics and intrinsic biomarkers to be measured) and measure concurrent environmental conditions, social experiences and individual characteristics.

We will use these data to measure individual variation in the onset and rate of senescence with unparalleled accuracy. We will quantify the impact of environmental, social, transgenerational (i.e. parental age) and genetic factors, across the genome, on when and how quickly individuals deteriorate with age. We will establish if trade-offs between different individual characteristics, and/or across different parts of an individual's life, determine patterns of senescence and whether there is a genetic basis to this. We will quantify the strength of selection on senescence. Finally, we will determine the overall relative impact that environmental, social, transgenerational and genetic effects have on individual senescence.

This study will not only test many key predictions that will reveal the immediate causes of individual variation in senescence, it will also shed light on the ultimate reasons behind the evolution of senescence. Understanding which factors exacerbate senescence means we can potentially avoid such factors or conditions, which will be directly useful to human/veterinary medicine, society and conservation.

Planned Impact

Our research will provide knowledge and understanding of how individuals differ in their senescence and how environmental, social, transgenerational and genetic effects influence this. As well as having a fundamental impact on scientific understanding and progress, our work and the translation of our results, will have potential widespread benefits for a number of groups including:

1. CONSERVATION MANAGERS: Optimise breeding programs of endangered species according to the environmental, social, transgenerational and genetic effects that our research finds impact on senescence negatively. An example is selecting breeding individuals according to their age to reduce transgenerational Lansing effects. Identify specific subpopulations best suited for translocations, e.g. individuals with reduced exposure to deleterious factors to mitigate senescent effects and / or using genomic selection.

2. THE SEYCHELLES: Stakeholders in Seychelles warbler (SW) conservation will gain a deeper understanding of the biology of the SW and can incorporate the results into plans for a fifth SW translocation. Facilitate public understanding and appreciation of science and conservation and help build capacity in these areas

3. ANIMAL BREEDERS: optimize breeding programs according to age and fluctuating environment effects; improve genetic diversity in controlled environments; provide information on the cellular mechanisms of senescence and the use of measures such as telomere length as a bio-marker of stress and senescence.

4. GENERAL PUBLIC: provide information on sources of individual variation in senescence rates, particularly how social, environmental, transgenerational and genetic effects can influence senescence. Offer age-appropriate explanations of SW senescence to children with underlying themes promoting both women in science and conservation of biodiversity. Biologists at undergraduate to post-graduate level will gain knowledge of the evolution of senescence.

5. MEDICAL AND NON-MEDICAL RESEARCHERS: provide a novel and holistic perspectives to biomedical scientists, demographers and researchers on senescence and help shape future medical research.

6. PUBLIC HEALTH POLICYMAKERS: provide information on potential long-term effects in future generations as a result of the increasing age at which individuals have children; guide future health care needs in populations with increasing numbers of senescing individuals; advise fecundity experts on effects of parental age at birth, and early social environment on senescence rates. All these factors will inform policies around healthy ageing.

7. PDRA/RA/TECHNICIAN: will gain valuable transferable skills sets that will advance their employability.

Using a combination of use of public/social media, workshops with SW stakeholders, talks at international conferences, an educational children's book, and strategic interactions with key stakeholders involved in setting the ageing research and policy agenda, we will maximise the impact of our research.

Publications

10 25 50
 
Description The CoIs published a peer-reviewed paper on how the environment plays an important role in the heritability of telomere length. We outline the factors known to impact telomere length and discuss the fact that telomere length is a trait that changes with age. We highlight statistical methods that can separate genetic from environmental effects and control for confounding variables. We then review how well previous studies in vertebrate populations including humans have taken these factors into account.



Following on from this review, the PI, CoIs and postdoc have been involved in two papers investigating the heritability of telomere length and parental age at conception effects on offspring telomere length, the first in the Seychelles warbler and the second in the European badger. In the European badger there was no evidence for parental age at conception effects while there were weak negative within-paternal age at conception effect in the Seychelles warbler (as fathers aged, their offspring had shorter telomeres). There was low heritability (contribution of additive genetic effects to total variation) of telomere length in the Seychelles warbler and no heritability in the European badger. These studies highlighted a low potential for evolutionary change in telomere length in these populations.



The CoIs and postdoc have also been involved in a further 2 papers in the Seychelles warbler population. The first assesses age-related changes in extra-pair paternity and found explicit evidence of senescence in infidelity in both males and females. The second paper shows how the presence of helpers at the nest can compensate for age-related declines in parental care and offspring survival.



The CoI has also been involved in a methods paper advising on the best approach for long-term studies in structuring samples for analysis. This paper used simulations to determine the best sample structuring strategy designed to separate confounding laboratory variation (among-batch and among-cluster variation) from biological variation for later statistical analyses.
Exploitation Route Our review paper raises awareness of the impact of the environment on estimates of telomere heritability, which is a much under-appreciated point. We conclude that we need larger studies, which also span longer time periods, to account for changing environmental effects, if we are to determine meaningful estimates of the genetic component of telomere length. This important point can be used by others planning to research telomere dynamics.



The two telomere heritability papers highlighted the need for longitudinal parental age at conception studies in the wild, and in studies estimating the heritability of telomere length the need for power analyses and accounting for experimental variation.



The extra-group paternity paper challenged the hypothesis that the association between male and extra-pair paternity was due to females seeking high-quality paternal genes for offspring.



The paper on parental care and offspring survival highlighted how alloparental care can alleviate fitness costs of senescence for breeders and that more studies need to investigate how early-life social environment can impact offspring performance.



The slicing approach put forward by the methods paper maximises the power of growing biobanks to address important ecological, epidemiological and evolutionary questions.
http://rstb.royalsocietypublishing.org/content/373/1741/20160450

https://onlinelibrary.wiley.com/doi/abs/10.1111/jeb.13728

https://onlinelibrary.wiley.com/doi/full/10.1111/mec.15804

https://onlinelibrary.wiley.com/doi/10.1111/mec.15563

https://onlinelibrary.wiley.com/doi/full/10.1002/evl3.213

https://besjournals.onlinelibrary.wiley.com/doi/full/10.1111/2041-210X.13352
Sectors Healthcare

URL http://rstb.royalsocietypublishing.org/content/373/1741/20160450
 
Title Slicing: A sustainable approach to structuring samples for analysis in long-term studies 
Description While the best approach to analysing long-term datasets depends on the structure of the data and questions of interest, it is vital to account for confounding among-cluster and batch variation. Our slicing approach is simple to apply and creates the necessary statistical independence of batch and cluster from environmental or biological variables of interest. Crucially, it allows sequential analysis of samples and flexible inclusion of current data in later analyses without completely confounding the analysis. Our approach maximizes the scientific value of every sample, as each will optimally contribute to unbiased statistical inference from the data. Slicing thereby maximizes the power of growing biobanks to address important ecological, epidemiological and evolutionary questions. 
Type Of Material Improvements to research infrastructure 
Year Produced 2020 
Provided To Others? Yes  
Impact n/a 
URL https://besjournals.onlinelibrary.wiley.com/doi/10.1111/2041-210X.13352
 
Title Data from: Socio-ecological conditions and female infidelity in the Seychelles warbler 
Description Within socially monogamous breeding systems, levels of extra-pair paternity can vary not only between species, populations and individuals, but also across time. Uncovering how different extrinsic conditions (ecological, demographic and social) influence this behavior will help shed light on the factors driving its evolution. Here, we simultaneously address multiple socio-ecological conditions potentially influencing female infidelity in a natural population of the cooperatively breeding Seychelles warbler, Acrocephalus sechellensis. Our contained study population has been monitored for over 25 years, enabling us to capture variation in socio-ecological conditions between individuals and across time and to accurately assign parentage. We test hypotheses predicting the influence of territory quality, breeding density and synchrony, group size and composition (number and sex of subordinates), and inbreeding avoidance on female infidelity. We find that a larger group size promotes the likelihood of extra-pair paternity in offspring from both dominant and subordinate females, but this paternity is almost always gained by dominant males from outside the group (not by subordinate males within the group). Higher relatedness between a mother and the dominant male in her group also results in more extra-pair paternity - but only for subordinate females - and this does not prevent inbreeding occurring in this population. Our findings highlight the role of social conditions favoring infidelity and contribute towards understanding the evolution of this enigmatic behavior. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact n/a 
URL http://datadryad.org/stash/dataset/doi:10.5061/dryad.h48d445
 
Title Data from: Telomere heritability and parental age at conception effects in a wild avian population 
Description Individual variation in telomere length is predictive of health and mortality risk across a range of species. However, the relative influence of environmental and genetic variation on individual telomere length in wild populations remains poorly understood. Heritability of telomere length has primarily been calculated using parent-offspring regression which can be confounded by shared environments. To control for confounding variables, quantitative genetic 'animal models' can be used, but few studies have applied animal models in wild populations. Furthermore, parental age at conception may also influence offspring telomere length, but most studies have been cross-sectional. We investigated within- and between- parental age at conception effects and heritability of telomere length in the Seychelles warbler using measures from birds caught over 20 years and a multi-generational pedigree. We found a weak negative within-paternal age at conception effect (as fathers aged, their offspring had shorter telomeres) and a weak positive between-maternal age at conception effect (females that survived to older ages had offspring with longer telomeres). Animal models provided evidence that heritability and evolvability of telomere length was low in this population, and that variation in telomere length was not driven by early-life effects of hatch period or parental identities. qPCR plate had a large influence on telomere length variation and not accounting for it in the models would have underestimated heritability. Our study illustrates the need to include and account for technical variation in order to accurately estimate heritability, as well as other environmental effects, on telomere length in natural populations. 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
Impact n/ 
URL http://datadryad.org/stash/dataset/doi:10.5061/dryad.vt4b8gtr1
 
Title Estimation of environmental, genetic and parental age at conception effects on telomere length in a wild mammal 
Description 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 and low evolvability ( 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
Impact Published paper 
URL http://datadryad.org/stash/dataset/doi:10.5061/dryad.dr7sqv9wr
 
Title Helpers compensate for age-related declines in parental care and offspring survival in a cooperatively breeding bird 
Description Offspring from elderly parents often have lower survival due to parental senescence. In cooperatively breeding species, where offspring care is shared between breeders and helpers, the alloparental care provided by helpers is predicted to mitigate the impact of parental senescence on offspring provisioning and, subsequently, offspring survival. We test this prediction using data from a long-term study on cooperatively breeding Seychelles warblers (Acrocephalus sechellensis). We find that the nestling-provisioning rate of female breeders declines with their age. Further, the total brood provisioning rate and the first-year survival probability of offspring decline progressively with age of the female breeder, but these declines are mitigated when helpers are present. This effect does not arise because individual helpers provide more care in response to the lower provisioning of older dominant females, but because older female breeders have recruited more helpers, thereby receiving more overall care for their brood. We do not find such effects for male breeders. These results indicate that alloparental care can alleviate the fitness costs of senescence for breeders, which suggests an interplay between age and cooperative breeding. 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
Impact Published paper 
URL http://datadryad.org/stash/dataset/doi:10.5061/dryad.rxwdbrv4s
 
Description Conference talk (BES 2019, Belfast) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Talk by PDRA Alex Sparks at the British Ecological Society Annual Meeting 2019 (11th December 2019 - Belfast) which initiated discussions on parental age effects on offspring fitness and the determinants of fitness in natural populations.
Year(s) Of Engagement Activity 2019
 
Description Conference talk (YUEG 2018, Sheffield) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Talk by PDRA Alex Sparks at the Yorkshire Universities Evolution Group meeting 2018 (25th June 2018 - Sheffield) which initiated discussions on the genetic basis of variation in telomere length and the use of quantitative genetic models to answer key questions in evolutionary biology.
Year(s) Of Engagement Activity 2018
 
Description ESEB 2019 presentation by H Dugdale 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact 1200 people attended ESEB 2020 and the poster was available to all
Year(s) Of Engagement Activity 2019
 
Description Seminar talk (BEE 2019, Leeds) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Talk by PDRA Alex Sparks at the Behaviour, Ecology & Evolution seminar series at the University of Leeds on 30th January 2019. The talk introduced postgraduate and undergraduate students to quantitative genetic techniques and initiated discussion on the heritability of telomere length in natural populations.
Year(s) Of Engagement Activity 2019
 
Description Wild Genomics Meeting - Bielefeld 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Talk by PDRA Alex Sparks at the Wild Genomics Meeting - Bielefeld, 07.03.18 - 09.03.18, which sparked discussions on the genomics of senescence
Year(s) Of Engagement Activity 2018