Transgenerational impacts on senescence: quantitative genetics of cellular and organismal ageing in the wild
Lead Research Organisation:
University of East Anglia
Department Name: Biological Sciences
Abstract
It has long been known that environmental factors, such as poor diet, can have considerable impact on an individuals' rate of ageing, however the possibility that these effects could be transmitted to the next generation, detrimentally impacting on ageing in offspring, or even grand offspring, has only recently been suggested.
Individuals of the same chronological age vary greatly in the rate at which they age biologically. Yet surprisingly we know little about how heritable the rate of biological ageing is, or how parental state can "carry-over" to influence offspring ageing - and even accumulate over generations to reduce population fitness and adaptive potential. Recent studies show that 'parental effects' are common and can be substantial, but the impact they have on senescence has not been explored.
We propose to integrate approaches from cellular biology and quantitative genetics, in an ecological setting, to investigate the strength and impact of trans-generational effects on cellular senescence (the biological condition of an organisms cells) - and the consequences of this for individual ageing and fitness in the wild. Within this we will investigate how key factors effecting parental state (e.g. age, genetic diversity, territory quality, malarial infection) contribute towards such trans-generational effects.
Mitochondria number and telomere length will be measured to assess inter and intra-individual variation in biological ageing. The loss of both telomeres and mitochondria is related to an increase in cellular and organismal senescence and a reduction in life expectancy. Importantly, mitochondrial genes have high mutation rates, which increase with age and in response to oxidative stress. As they are also non-recombinant and maternally inherited, they are vulnerable to the accumulation of mutations across generations. In contrast, telomere inheritance is nuclear and bi-parentally inherited and, intriguingly, telomeres may increase in length, in sperm, with paternal age. The different inheritance of these factors creates the possibility that genetic and parental effects may differ through the male and female line, and provides us with the ability to assess such sex-specific effects.
This study will measure how much variation in biological ageing rate is explained by "genetic quality" and "parental state" - and investigate how selection acts upon these traits over multiple generations in the wild. Such longitudinal studies have not previously been possible in free-living vertebrates, given their long life-spans and the lack of techniques with which to investigate cellular senescence. However, the long-term study of an entire, isolated, population of Seychelles warblers now provides an excellent opportunity to do so because;
1. We have a powerful, genetically verified, multi-generational pedigree for this population
2. Repeat blood samples taken throughout the birds' lives allow for individual rates of telomere and mitochondrial change to be measured (ca. 3,500 samples).
3. Survival, fecundity and age data are unconfounded by dispersal, which is extremely rare in natural systems
4. Adults lack natural predators, thus ageing processes can be studied without excessive extrinsic mortality reducing sample size and confounding results
5. We have extensive detailed individual information on genetic and environmental factors, allowing us to isolate drivers of parental effects
The research outcomes from this novel study will help identify the effect parents have, in terms of senescence patterns, on the lives of their offspring. They will also help us understand the extraordinary variation in longevity and senescence observed between and within species in nature allowing us to understand the fundamental factors shaping the evolution of senescence.
Individuals of the same chronological age vary greatly in the rate at which they age biologically. Yet surprisingly we know little about how heritable the rate of biological ageing is, or how parental state can "carry-over" to influence offspring ageing - and even accumulate over generations to reduce population fitness and adaptive potential. Recent studies show that 'parental effects' are common and can be substantial, but the impact they have on senescence has not been explored.
We propose to integrate approaches from cellular biology and quantitative genetics, in an ecological setting, to investigate the strength and impact of trans-generational effects on cellular senescence (the biological condition of an organisms cells) - and the consequences of this for individual ageing and fitness in the wild. Within this we will investigate how key factors effecting parental state (e.g. age, genetic diversity, territory quality, malarial infection) contribute towards such trans-generational effects.
Mitochondria number and telomere length will be measured to assess inter and intra-individual variation in biological ageing. The loss of both telomeres and mitochondria is related to an increase in cellular and organismal senescence and a reduction in life expectancy. Importantly, mitochondrial genes have high mutation rates, which increase with age and in response to oxidative stress. As they are also non-recombinant and maternally inherited, they are vulnerable to the accumulation of mutations across generations. In contrast, telomere inheritance is nuclear and bi-parentally inherited and, intriguingly, telomeres may increase in length, in sperm, with paternal age. The different inheritance of these factors creates the possibility that genetic and parental effects may differ through the male and female line, and provides us with the ability to assess such sex-specific effects.
This study will measure how much variation in biological ageing rate is explained by "genetic quality" and "parental state" - and investigate how selection acts upon these traits over multiple generations in the wild. Such longitudinal studies have not previously been possible in free-living vertebrates, given their long life-spans and the lack of techniques with which to investigate cellular senescence. However, the long-term study of an entire, isolated, population of Seychelles warblers now provides an excellent opportunity to do so because;
1. We have a powerful, genetically verified, multi-generational pedigree for this population
2. Repeat blood samples taken throughout the birds' lives allow for individual rates of telomere and mitochondrial change to be measured (ca. 3,500 samples).
3. Survival, fecundity and age data are unconfounded by dispersal, which is extremely rare in natural systems
4. Adults lack natural predators, thus ageing processes can be studied without excessive extrinsic mortality reducing sample size and confounding results
5. We have extensive detailed individual information on genetic and environmental factors, allowing us to isolate drivers of parental effects
The research outcomes from this novel study will help identify the effect parents have, in terms of senescence patterns, on the lives of their offspring. They will also help us understand the extraordinary variation in longevity and senescence observed between and within species in nature allowing us to understand the fundamental factors shaping the evolution of senescence.
Planned Impact
This proposal investigates trans-generational impacts on ageing in a natural population. Knowledge and understanding will be gained on how the age, condition or experiences of parents influence the quality, health and ageing profiles of offspring. This will clearly be of interest far beyond the realm of evolutionary biology.
Key beneficiaries and how they will benefit
Medical researchers will gain by understanding how the specific cellular mechanisms examined (mitochondrial number, Telomere shortening) impact upon the health and survival of individuals, and their offspring. This may help focus future medical research appropriately.
Human health authorities keen to know what long-term effects they may expect in future generations as a result of the increasing average age of parents. Or for that matter, how improved parental conditions (reduced stress, improved diet etc.) may positively affect offspring. This will allow them focus medical advice and plan for future health care needs, both of which would benefit society.
Human fertility treatment specialists, e.g. assisting the reproduction of older individuals, will gain insight into when and how offspring produced may be affected by the age/condition of their parents.
Animal breeders/farmers will benefit by knowing what effects, in terms of individual quality and longevity, breeding from parents in, or under, certain conditions may have, thus allowing them to modify breeding programmes, or the conditions in which breeding stock are kept, to maximise long-term output and animal welfare.
Conservation policymakers/practitioners will also benefit from understanding what effect breeding from parents in, or under, certain conditions may have and, importantly, how this may impact overall population growth and viability. It could inform them of how best to manage endangered species breeding programs or translocation policies (e.g. avoiding old or stressed individuals) to minimise impacts on individual health or future population viability.
Academic researchers in other areas of science could benefit by understanding the ramifications, in terms of organismal condition and survival, of the cellular processes that we focus on here and which many of them work on in much greater detail in the laboratory. This will, hopefully, provide them with a novel holistic and evolutionary perspective. It would also help inform the whole area of ageing research by providing a 'natural' multi-generational perspective on vertebrate ageing.
Communicating to the widest possible audience is important to maximise the economic and societal benefits of this research, a goal that both the individual researcher involved, and the School of Biological sciences at UEA, are strongly committed to (for further details, see Pathways to Impact).
Key beneficiaries and how they will benefit
Medical researchers will gain by understanding how the specific cellular mechanisms examined (mitochondrial number, Telomere shortening) impact upon the health and survival of individuals, and their offspring. This may help focus future medical research appropriately.
Human health authorities keen to know what long-term effects they may expect in future generations as a result of the increasing average age of parents. Or for that matter, how improved parental conditions (reduced stress, improved diet etc.) may positively affect offspring. This will allow them focus medical advice and plan for future health care needs, both of which would benefit society.
Human fertility treatment specialists, e.g. assisting the reproduction of older individuals, will gain insight into when and how offspring produced may be affected by the age/condition of their parents.
Animal breeders/farmers will benefit by knowing what effects, in terms of individual quality and longevity, breeding from parents in, or under, certain conditions may have, thus allowing them to modify breeding programmes, or the conditions in which breeding stock are kept, to maximise long-term output and animal welfare.
Conservation policymakers/practitioners will also benefit from understanding what effect breeding from parents in, or under, certain conditions may have and, importantly, how this may impact overall population growth and viability. It could inform them of how best to manage endangered species breeding programs or translocation policies (e.g. avoiding old or stressed individuals) to minimise impacts on individual health or future population viability.
Academic researchers in other areas of science could benefit by understanding the ramifications, in terms of organismal condition and survival, of the cellular processes that we focus on here and which many of them work on in much greater detail in the laboratory. This will, hopefully, provide them with a novel holistic and evolutionary perspective. It would also help inform the whole area of ageing research by providing a 'natural' multi-generational perspective on vertebrate ageing.
Communicating to the widest possible audience is important to maximise the economic and societal benefits of this research, a goal that both the individual researcher involved, and the School of Biological sciences at UEA, are strongly committed to (for further details, see Pathways to Impact).
Publications
Dugdale HL
(2018)
Heritability of telomere variation: it is all about the environment!
in Philosophical transactions of the Royal Society of London. Series B, Biological sciences
Bebbington K
(2017)
Kinship and familiarity mitigate costs of social conflict between Seychelles warbler neighbors.
in Proceedings of the National Academy of Sciences of the United States of America
Fairfield EA
(2016)
The impact of conservation-driven translocations on blood parasite prevalence in the Seychelles warbler.
in Scientific reports
Hammers M
(2016)
Age-specific haemosporidian infection dynamics and survival in Seychelles warblers.
in Scientific reports
Busana M
(2022)
Population level consequences of facultatively cooperative behaviour in a stochastic environment.
in The Journal of animal ecology
Spurgin LG
(2018)
Spatio-temporal variation in lifelong telomere dynamics in a long-term ecological study.
in The Journal of animal ecology
Groenewoud F
(2018)
Subordinate females in the cooperatively breeding Seychelles warbler obtain direct benefits by joining unrelated groups.
in The Journal of animal ecology
Description | Telomeres can be used as a generic currency to assess how well an individual is able to cope with the environment it lives in. Inbred individual suffer greater telomere damage under poor conditions than outbred individuals. Importantly this impact can be transgenerational: the offspring from inbred mothers suffer greater telomere attrition. Other finding show that telomeres can be used to measure the often normally hidden impact of other stresses - including antagonistic interactions with neighbours. One later key finding is that contrary to perceived wisdom telomeres can show extension as well as attrition within the lifespan of wild living organims. |
Exploitation Route | Using telomeres as biomarkers of the impact of external factors on individuals. Assessing the impact of stressful environments |
Sectors | Agriculture, Food and Drink,Environment,Healthcare |
Description | Gut microbiome variation, fitness and senescence within a natural vertebrate population |
Amount | £604,262 (GBP) |
Funding ID | NE/S010939/1 |
Organisation | Natural Environment Research Council |
Sector | Public |
Country | United Kingdom |
Start | 02/2020 |
End | 10/2024 |
Description | NERC standard Grants |
Amount | £789,000 (GBP) |
Funding ID | NE/P011284/1 |
Organisation | Natural Environment Research Council |
Sector | Public |
Country | United Kingdom |
Start | 11/2017 |
End | 10/2020 |
Title | Data from: Contemporary evolution of the innate immune receptor gene TLR3 in an isolated vertebrate population |
Description | Understanding where genetic variation exists, and how it influences fitness within populations is important from an evolutionary and conservation perspective. Signatures of past selection suggest that pathogen-mediated balancing selection is a key driver of immunogenetic variation, but studies tracking contemporary evolution are needed to help resolve the evolutionary forces and mechanism at play. Previous work in a bottlenecked population of Seychelles warblers (Acrocephalus sechellensis) show that functional variation has been maintained at the viral-sensing Toll-like receptor 3 (TLR3) gene, including one non-synonymous SNP, resulting in two alleles. Here, we characterise evolution at this TLR3 locus over a 25-year period within the original remnant population of the Seychelles warbler, and in four other derived, populations. Results show a significant and consistent temporal decline in the frequency of the TLR3C allele in the original population, and that similar declines in the TLR3C allele frequency occurred in all the derived populations. Individuals (of both sexes) with the TLR3CC genotype had lower survival, and males - but not females - that carry the TLR3C allele had significantly lower lifetime reproductive success than those with only the TLR3A allele. These results indicate that positive selection, caused by an as yet unknown agent, is driving TLR3 evolution in the Seychelles warblers. No evidence of heterozygote advantage was detected. However, whether the positive selection observed is part of a longer-term pattern of balancing selection (through fluctuating selection or rare-allele advantage) cannot be resolved without tracking the TLR3C allele in the populations over an extended period of time. |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
URL | http://datadryad.org/stash/dataset/doi:10.5061/dryad.m905qfv06 |
Title | Data from: Sex-dependent effects of parental age on offspring fitness in a cooperatively breeding bird |
Description | Parental age can have considerable effects on offspring phenotypes and health. However, intergenerational effects may also have longer-term effects on offspring fitness. Few studies have investigated parental age effects on offspring fitness in natural populations while also testing for sex- and environment-specific effects. Further, longitudinal parental age effects may be masked by population-level processes such as the selective disappearance of poor-quality individuals. Here, we used multi-generational data collected on individually marked Seychelles warblers (Acrocephalus sechellensis) to investigate the impact of maternal and paternal age on offspring lifespan and lifetime reproductive success. We found negative effects of maternal age on female offspring lifespan and lifetime reproductive success, which were driven by within-mother effects. There was no difference in annual reproductive output of females born to older versus younger mothers, suggesting that the differences in offspring lifetime reproductive success were driven by effects on offspring lifespan. In contrast, there was no association between paternal age and female offspring lifespan or either maternal or paternal age and male offspring lifespan. Lifetime reproductive success, but not annual reproductive success, of male offspring increased with maternal age, but this was driven by between-mother effects. No paternal age effects were found on female offspring's lifetime reproductive success but there was a positive between-father effect on male offspring's lifetime reproductive success. We did not find strong evidence for environment-dependent parental age effects. Our study provides evidence for parental age effects on the lifetime fitness of offspring and shows that such effects can be sex-dependent. These results add to the growing literature indicating the importance of intergenerational effects on long-term offspring performance and highlight that these effects can be an important driver of variation in longevity and fitness in the wild. |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
URL | http://datadryad.org/stash/dataset/doi:10.5061/dryad.7d7wm37zc |
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 |
URL | http://datadryad.org/stash/dataset/doi:10.5061/dryad.vt4b8gtr1 |
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 |
URL | http://datadryad.org/stash/dataset/doi:10.5061/dryad.rxwdbrv4s |
Title | Seychelles warbler database |
Description | an access database of all the information collected by the international seychelles warbler group over the last 15 years incvluding the behavioural fitness and genetic data |
Type Of Material | Database/Collection of data |
Year Produced | 2006 |
Provided To Others? | Yes |
Impact | additional long term research above and beyond that outlined in the original grants |
Title | Structural equation modeling reveals determinants of fitness in a cooperatively breeding bird |
Description | Even in well-studied organisms, it is often challenging to uncover the social and environmental determinants of fitness. Typically, fitness is determined by a variety of factors that act in concert, thus forming complex networks of causal relationships. Moreover, even strong correlations between social and environmental conditions and fitness components may not be indicative of direct causal links, as the measured variables may be driven by unmeasured (or unmeasurable) causal factors. Standard statistical approaches, like multiple regression analyses, are not suited for disentangling such complex causal relationships. Here, we apply structural equation modeling (SEM), a technique that is specifically designed to reveal causal relationships between variables, and which also allows to include hypothetical causal factors. Therefore, SEM seems ideally suited for comparing alternative hypotheses on how fitness differences arise from differences in social and environmental factors. We apply SEM to a rich data set collected in a long-term study on the Seychelles warbler (Acrocephalus seychellensis), a bird species with facultatively cooperative breeding and a high rate of extra-group paternity. Our analysis reveals that the presence of helpers has a positive effect on the reproductive output of both female and male breeders. In contrast, per capita food availability does not affect reproductive output. Our analysis does not confirm earlier suggestions on other species that the presence of helpers has a negative effect on the reproductive output of male breeders. As such, both female and male breeders should tolerate helpers in their territories, irrespective of food availability. |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
URL | http://datadryad.org/stash/dataset/doi:10.5061/dryad.jm63xsjc6 |
Description | Diversity in Telomeres group |
Organisation | University of Edinburgh |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | on organising body for the Diversity in Telomeres group - contributing to symposia, workshops and journal special issues to generate growth and understanding in this field |
Collaborator Contribution | on organising body for the Diversity in Telomeres group - contributing to symposia, workshops and journal special issues to generate growth and understanding in this field |
Impact | annual diversity in telomeres conference special issue of Philosophical transactions of the london society Journal |
Start Year | 2015 |
Description | Diversity in Telomeres group |
Organisation | University of Glasgow |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | on organising body for the Diversity in Telomeres group - contributing to symposia, workshops and journal special issues to generate growth and understanding in this field |
Collaborator Contribution | on organising body for the Diversity in Telomeres group - contributing to symposia, workshops and journal special issues to generate growth and understanding in this field |
Impact | annual diversity in telomeres conference special issue of Philosophical transactions of the london society Journal |
Start Year | 2015 |
Description | Diversity in Telomeres group |
Organisation | University of Groningen |
Country | Netherlands |
Sector | Academic/University |
PI Contribution | on organising body for the Diversity in Telomeres group - contributing to symposia, workshops and journal special issues to generate growth and understanding in this field |
Collaborator Contribution | on organising body for the Diversity in Telomeres group - contributing to symposia, workshops and journal special issues to generate growth and understanding in this field |
Impact | annual diversity in telomeres conference special issue of Philosophical transactions of the london society Journal |
Start Year | 2015 |
Description | Seychelles Warbler Research Group |
Organisation | University of Groningen |
Department | Groningen Institute for Evolutionary Life Sciences |
Country | Netherlands |
Sector | Academic/University |
PI Contribution | We collaborate on running and using this long term model system. And the database that results from that. Fieldwork, key genetical data (MHC, Telomere, genotyping) |
Collaborator Contribution | Field work Molecular expertise Long term data Molecular Data Database management |
Impact | All the papers we produce are , to a greater or lesser degree, the result of this collaboration on mainlining this long term system |
Description | Seychelles Warbler Research Group |
Organisation | University of Sheffield |
Department | Department of Molecular Biology and Biotechnology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We collaborate on running and using this long term model system. And the database that results from that. Fieldwork, key genetical data (MHC, Telomere, genotyping) |
Collaborator Contribution | Field work Molecular expertise Long term data Molecular Data Database management |
Impact | All the papers we produce are , to a greater or lesser degree, the result of this collaboration on mainlining this long term system |
Description | Aalborg Zoo meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | research presentation at a Zoo. to researchers and management and public |
Year(s) Of Engagement Activity | 2016 |
Description | Nature Seychelles Magazine |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Third sector organisations |
Results and Impact | Articles and blogs in the Seychelles conservation Magazine |
Year(s) Of Engagement Activity | 2013,2014,2015,2016 |
Description | stage show as part of the science festival in Norwich |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | stage comedy show - 'Did the victorians ruin the world. one bit focused on Darwin and how understanding evolution may have changed the world |
Year(s) Of Engagement Activity | 2018 |
URL | https://norwichsciencefestival.co.uk/events/did-the-victorians-ruin-the-world/ |