Periodic Reporting for period 2 - InterAge (Intergenerational transfer of ageing: effects of maternal age at breeding on offspring performance)
Periodo di rendicontazione: 2023-05-01 al 2024-10-31
Ageing research has primarily focused on somatic deterioration of individuals during their lifetimes; intergenerational effects have been little studied. In this project I address this gap, in the process bringing together currently discrete lines of research from evolutionary ecology and reproductive biology. A large body of research in population biology shows that there can be a negative relationship between parental age at breeding and offspring lifespan. It has been postulated that the magnitude of the effect is exacerbated when offspring experience harsher conditions, particularly in early life. The causes and time-course of this so-called ‘Lansing effect’ are unclear - is it due to higher lifetime frailty of offspring, a faster ageing rate, or both, and how is it affected by the environmental conditions that they face? Telomere loss and mitochondrial dysfunction in somatic cells are two recognized, interconnected, ‘Hallmarks of Ageing’ linked to individual performance and longevity. Experimental work, mostly in fertility research, has shown that the eggs of older mothers frequently have reduced mitochondrial function and shorter average telomere lengths. The life-course outcome of this impairment for the offspring has not been studied. Using the zebra finch, this challenging, high-gain, project tests for the first time the hypothesis that the negative effect of maternal age on offspring performance and ageing rate is due to lifelong, intertwined changes in offspring mitochondrial function and telomere length, and is exacerbated in offspring experiencing increased early life stress. Knowing why, when, and under what conditions maternal age has a negative effect on offspring health and longevity has important implications for our understanding of ageing, life history evolution, reproductive scheduling and mate choice; it also has profound consequences for more applied fields such as reproductive medicine and conservation biology. We are testing this is a long-term study of the performance and biological state of offspring from young and old mothers using a small bird that breeds well in captivity, the zebra finch.
Work over the first 30 months has focused on appointing staff and then breeding old and young female zebra finches with young males. That all the mothers breed with young males ensures that we do not have additional effects due to paternal age, since we know these can occur. Our project is particularly concerned with the effects of mitochondrial function, and the focus on mothers is because mitochondrial in offspring are inherited only from the mother. We have measured various aspects of biological state in the mothers, including flight performance, metabolic parameters and mitochondrial function. We have also published a paper showing that mitochondrial function declines with age in our study species. As important part of the project tests the prediction that the effects of having an old mother are exacerbated if the young are exposed to stressful circumstances in early life. Therefore, half of the offspring from both young and old mothers have been exposed to relatively mild stress (equivalent to being scared by a predator twice per day). This was done by manipulating their stress hormones. We are now following the four groups of offspring from these mothers and tracking changes in their performance from young to old age. We have developed methods to measure their biological state, with a focus on locomotory performance, as is the case for measures of frailty in humans. We are looking at how fast they age and how their reproductive capacity changes, testing the prediction that offspring of older mothers age faster. We are also measuring a number of molecular and physiological parameters that change with age as we did in their mothers. In addition, one of the post-doctoral researchers and the Principal Investigator have published an extensive review on the evolution of post-reproductive lifespan, with a focus on the importance of mitochondrial function. Post reproductive lifespan is where individuals survive beyond the age at which reproduction occurs, as in the menopause of the human female. We put forward a new hypothesis that post reproductive lifespan evolves in animals which have large, energy expensive brains that they need for living in complex social networks; any decline in the functioning of the mitochondria the offspring inherit from their mother substantially reduces offspring fitness to a point where it is no longer worth the female breeding. However, she can still contribute to the biological fitness of the offspring she has already produced.
Our work on mitochondrial function in relation to age and how mitochondria inherited from older mothers might affect offspring health, is challenging and beyond the state of the art. We are developing advanced methodology to measure mitochondrial function from early embryos to later adulthood. WE are testing the prediction that the offspring of older mothers will age faster than those of younger mothers, especially when the offspring have experience additional stress in early life. We anticipate that this will be the case.