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Lifelong health, markers of ageing and senescence in a long-lived mammal.

Periodic Reporting for period 1 - AGEISM (Lifelong health, markers of ageing and senescence in a long-lived mammal.)

Reporting period: 2016-01-01 to 2017-12-31

The ageing populations of most European countries involve major health, economic and social consequences. It is thus critical to understand the limitations of deferring the negative effects of ageing and the mechanisms involved in growing old. Improving the quality of life at old age in humans and predicting future changes in longevity patterns of societies might depend on our ability to develop indicators of how old we really are and how many healthy years we have ahead of us, and how those indicators depend on our health history across decades. Such efforts for reducing the impact of senescence in humans might be best investigated in equally long-lived animals. The aim of this fellowship was to improve our understanding of the factors that cause some individuals to age faster than others and influence ageing patterns, and to better grasp both the mechanisms of ageing and their consequences on senescence rates in long-lived species. To do so, I used innovative approaches by combining the study of senescence patterns to ageing mechanisms and how they interact with variations in lifelong health and stress status, and endocrinological measures of stress in Asian elephants. Overall, this Marie Curie Fellowship has resulted in the understanding of the variation in senescence patterns, its links to ageing rates and stress levels, but also to better understand ageing mechanisms and their consequences on senescence rates, in a long-lived species as humans.
The substantial data and biological samples that have been collected through this project have contributed significantly to our understanding of the factors shaping senescence patterns in the Asian elephant, while paving the way for more in-depth molecular analyses. These analyses - which are currently underway - will help to better understand the underlying mechanisms of such patterns and to establish ageing markers as a potential health marker. My results will also contribute to provide new solutions to elephant management and healthcare.
During this fellowship, I conducted work using demographic, molecular and physiological data on Asian elephants in Myanmar. I contributed to strengthen the world’s largest studbook on elephants, by collecting, for each individual, data on date, place of birth/death, age, filiation, and origin. This represents the most comprehensive demographic data for any elephant population worldwide. I also collected physical measures (body weight, size, body condition), health and disease records, as well as blood and feacal samples to measure a range of molecular and physiological data. Blood samples were used to measure oxidative stress and telomere dynamics; faecal samples were used to assess parasites load and cortisol levels. While, thanks to our collaboration with the Chiang Mai University, measures of the levels of endocrinological stress and of parasites intensities were already optimized; I had to establish protocols to measure oxidative stress in elephants, to extract DNA, and to optimize qPCR telomere assays for elephant samples. Completion of these analyses is expected within the coming months.

The demographic data collected allowed me to determine factors influencing senescence patterns in the elephant population. First, I examined the effects of advanced maternal age at birth on offspring condition, age-specific reproductive success, and long-term survival. I show that offspring born to older mothers display reduced overall survival and higher age-specific reproductive success, but reduced survival of their own progeny. My results show rare evidence of a persistent effect of maternal age on fitness across generations in a long-lived mammalian population.
I then was interested in investigating how differential sex allocation might impact offspring condition, age-specific reproductive success, and long-term survival. I show that calves born after a male sibling display reduced body mass and lower survival compared with those born after females. The sex of the previous offspring also seems to impact the reproduction of the subsequent siblings, with females born after a male sibling reproducing more slowly. This is the first time such a long-term intergenerational cost has been shown in a mammal species.

Although senescence is often observed in the wild, its underlying mechanistic causes are still poorly understood. I was thus also interested in investigating age-related variations in biological markers of health and their interconnectedness with variations in environmental conditions. I examined how different physiological markers of health (body score index, blood cells count, liver and kidney functions) vary across age. In this study, we see a decline of body condition, immune and liver functions with age; which is the first evidence of senescence on physiological traits in Asian elephants.

The results of this project have been presented at several national and international conferences, including evolutionary biology and physiology symposiums in 2017, as well as invited talks in different Universities (Glasgow – Scotland, Turku – Finland) in 2016 and 2017, which were ideal opportunities to present my research to a broad range of scientists (from ecologists to epidemiologists) interested senescence and its mechanisms.
This fellowship has yielded unprecedented data and material for improving our understanding of the senescence patterns and the physiological processes involved in a long-lived species such as ourselves. By providing insights on the role of molecular and physiological markers in evolutionary processes, by identifying how they interact with variations in health and stress status and how they determine ageing rates and individual variation in senescence rates, my results will significantly improve our comprehension of the evolution of lifespan. These results pave the way to establish which molecular markers best represent individual health history and to understand how health history can predict ageing rates. Such findings will provide invaluable insights applicable beyond evolutionary biology. For instance in conservation biology, as identifying the mechanisms by which stress and births reduce health, survival and breeding rates of the working elephants will help to provide new solutions to elephant management and healthcare. Indeed, sustaining the timber elephants is important not only for Asian elephants, but for the wider ecosystem in the region. Therefore, drawn from our recent research, we presented recommendations on elephant health, as well as on birth and death rates, for the management and future research of timber elephants in Myanmar.
Finally, the outcomes of this fellowship have led to securing a further 3 years of fellowship funding (TCSM Fellowship at the University of Turku, Finland) for ongoing research in this area.
Field work in Myanmar