Transgenerational impacts on senescence: quantitative genetics of cellular and organismal ageing in the wild

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.

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).