Periodic Reporting for period 4 - Elephant Project (How elephants grow old)
Période du rapport: 2020-07-01 au 2021-12-31
The ageing population structure of most European countries has major health, economic and social consequences that lead to a need to better understand both the evolutionary limitations of deferring ageing, as well as the mechanisms involved in growing old. Ageing involves reduced fertility, mobility and ability to combat disease, but some individuals cope with growing old better than others.
Improving the quality of life at old age 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, and how those indicators depend on our health history across several decades. Yet, most model species used in biology are short-lived and provide a poor comparison to long-lived mammals such as humans. Further, they do not often inform on the mechanisms of ageing alongside its fitness consequences in natural populations of long-lived mammals.
Elephant project integrates different ageing mechanisms with unique data on lifelong disease and reproductive history in the most long-lived non-human mammal studied so far, the Asian elephant. The project team will examine how different mechanisms of ageing (telomere dynamics, oxidative stress and telomerase activity) interact with lifelong disease and reproductive history, and current endocrinological measures of stress and reproductive status. This will help to better understand both the mechanisms of ageing and their consequences on senescence rates.
Understanding changes in health across life and its links to ageing rates, stress levels and life-history in a species as long-lived as humans will be relevant to a large range of end-users.
Improving the quality of life at old age 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, and how those indicators depend on our health history across several decades. Yet, most model species used in biology are short-lived and provide a poor comparison to long-lived mammals such as humans. Further, they do not often inform on the mechanisms of ageing alongside its fitness consequences in natural populations of long-lived mammals.
Elephant project integrates different ageing mechanisms with unique data on lifelong disease and reproductive history in the most long-lived non-human mammal studied so far, the Asian elephant. The project team will examine how different mechanisms of ageing (telomere dynamics, oxidative stress and telomerase activity) interact with lifelong disease and reproductive history, and current endocrinological measures of stress and reproductive status. This will help to better understand both the mechanisms of ageing and their consequences on senescence rates.
Understanding changes in health across life and its links to ageing rates, stress levels and life-history in a species as long-lived as humans will be relevant to a large range of end-users.
The project started in January 2016 with monthly field data collection on elephant biosamples and demographic parameters in Myanmar, with the goal of compiling a unique combination of monthly biodata and demographic data on this rare model of ageing patterns in extremely long-lived mammals. Although both covid19 and the critically changed political situation in Myanmar during the project duration posed major challenges to some of the project aims, over the entire project duration, the team completed the extraction and lab analysis of almost all samples, health parameters and ageing-rate measures collected.
The team in Turku then conducted extensive statistical analysis of these data to address the project main scientific aims. These analyses have led, for example, to the following major discoveries:
1. By using the multigenerational demographic dataset of our semi-captive Asian elephants combined with measures of body size, we have quantified how maternal age affects offspring condition, age-specific reproductive success and long-term survival. We show that offspring born to older mothers display reduced overall survival, and higher age-specific reproductive success, but reduced survival of their own progeny. Our results suggest a persistent effect of maternal age on fitness across generations for the first time in a naturally occurring mammalian population.
2. We have also found that grandcalves from young mothers (<20 years) had 8 times lower mortality risk if the grandmother resided with her grandcalf compared to grandmothers residing elsewhere. Resident grandmothers also decreased their daughters’ inter-birth intervals by one year. Our findings that grandmother’s presence was highly beneficial for grandcalf survival particularly among young mothers and the daughters were also able to reproduce more rapidly in the presence of their mothers in elephants have implications for our understanding of the evolution and selection pressures on post-reproductive lifespan in general, as well as on dispersal and social system in elephants specifically.
3. Our extensive data on health, molecular and physiological measures of senescence have allowed determining the underlying mechanistic causes of senescence alongside its consequences. Although documenting how different age-related changes in health accelerate ageing at a mechanistic level is key if we are to better understand the ageing process, few studies, particularly on natural populations of long-lived animals, have investigated age-related variation in biological markers of health and sex differences therein. We showed that pronounced differences in haematology, blood chemistry, immune, and liver functions among age classes are also evident under natural conditions in this extremely long-lived mammal. We provide strong support that overall health declined with age, with progressive declines in immune and liver functions similarly in both males and females. These changes parallel those mainly observed to-date in humans and laboratory mammals, and suggest a certain ubiquity in the ageing patterns.
4. We have also shown that wild-captured elephants, suffering from adverse early events, had markedly lower survival and reproduction compared to captive-born elephants in timber camps, and that the harmful effects of capture on survival lasted for several years or even decades. In parallel, we have shown the mechanistic basis for such effects, documenting in detail how adverse early-life stress in the form of taming affects health, physiological measures of ageing and stress longitudinally.
These and other results have been published thus far in 30 peer-reviewed articles, including high-impact publications e.g. in Nature Communications, and with several further articles currently in press, under review, and in preparation. They have also been widely disseminated in press releases, social media, and presentations ranging from The World Economic Forum, SLUSH and scientific conferences to primary schools and other broad public events.
The team in Turku then conducted extensive statistical analysis of these data to address the project main scientific aims. These analyses have led, for example, to the following major discoveries:
1. By using the multigenerational demographic dataset of our semi-captive Asian elephants combined with measures of body size, we have quantified how maternal age affects offspring condition, age-specific reproductive success and long-term survival. We show that offspring born to older mothers display reduced overall survival, and higher age-specific reproductive success, but reduced survival of their own progeny. Our results suggest a persistent effect of maternal age on fitness across generations for the first time in a naturally occurring mammalian population.
2. We have also found that grandcalves from young mothers (<20 years) had 8 times lower mortality risk if the grandmother resided with her grandcalf compared to grandmothers residing elsewhere. Resident grandmothers also decreased their daughters’ inter-birth intervals by one year. Our findings that grandmother’s presence was highly beneficial for grandcalf survival particularly among young mothers and the daughters were also able to reproduce more rapidly in the presence of their mothers in elephants have implications for our understanding of the evolution and selection pressures on post-reproductive lifespan in general, as well as on dispersal and social system in elephants specifically.
3. Our extensive data on health, molecular and physiological measures of senescence have allowed determining the underlying mechanistic causes of senescence alongside its consequences. Although documenting how different age-related changes in health accelerate ageing at a mechanistic level is key if we are to better understand the ageing process, few studies, particularly on natural populations of long-lived animals, have investigated age-related variation in biological markers of health and sex differences therein. We showed that pronounced differences in haematology, blood chemistry, immune, and liver functions among age classes are also evident under natural conditions in this extremely long-lived mammal. We provide strong support that overall health declined with age, with progressive declines in immune and liver functions similarly in both males and females. These changes parallel those mainly observed to-date in humans and laboratory mammals, and suggest a certain ubiquity in the ageing patterns.
4. We have also shown that wild-captured elephants, suffering from adverse early events, had markedly lower survival and reproduction compared to captive-born elephants in timber camps, and that the harmful effects of capture on survival lasted for several years or even decades. In parallel, we have shown the mechanistic basis for such effects, documenting in detail how adverse early-life stress in the form of taming affects health, physiological measures of ageing and stress longitudinally.
These and other results have been published thus far in 30 peer-reviewed articles, including high-impact publications e.g. in Nature Communications, and with several further articles currently in press, under review, and in preparation. They have also been widely disseminated in press releases, social media, and presentations ranging from The World Economic Forum, SLUSH and scientific conferences to primary schools and other broad public events.
The most novel and unconventional outcome from the Elephant Project is the multi-faceted, unique dataset itself that we have built for the use of cross-disciplinary research. Data collected include combining:
First, lifelong record of health and disease
Second, birth size, or subsequent individual size or body condition
Third, group (family) compositions
Fourth, reproductive and stress hormone samples, physiological ageing measures, parasite infection levels, longitudinal health monitoring including hematology, serum chemistry and clinical examination, and milk quality
Fifth, individual life-history data such as start of reproduction, lifelong records of births, death and its cause
Sixth, behavioural differences, personality variation and working task assays
Seventh, genomic data on e.g. inbreeding level and specific genetic markers
Using these data, we have been the first to determine how complementary measures of current health during 2011-2020 associate with ageing rates.
We have then examined how health at given ages across life and cumulatively across previous life are related to different physiological measures of ageing.
We have revealed how reproductive investment and early stress affects the age-specific health status and increase in disease prevalence over entire lifespan of females. We also show how past reproduction is linked to a complementary correlates of current health, condition and ageing rate, measured by body mass and score, stress hormones and ageing markers.
We have also produced the first high-quality reference genome for Asian elephant that is currently being prepared for publication, and genotyped 300 of our study animals.
First, lifelong record of health and disease
Second, birth size, or subsequent individual size or body condition
Third, group (family) compositions
Fourth, reproductive and stress hormone samples, physiological ageing measures, parasite infection levels, longitudinal health monitoring including hematology, serum chemistry and clinical examination, and milk quality
Fifth, individual life-history data such as start of reproduction, lifelong records of births, death and its cause
Sixth, behavioural differences, personality variation and working task assays
Seventh, genomic data on e.g. inbreeding level and specific genetic markers
Using these data, we have been the first to determine how complementary measures of current health during 2011-2020 associate with ageing rates.
We have then examined how health at given ages across life and cumulatively across previous life are related to different physiological measures of ageing.
We have revealed how reproductive investment and early stress affects the age-specific health status and increase in disease prevalence over entire lifespan of females. We also show how past reproduction is linked to a complementary correlates of current health, condition and ageing rate, measured by body mass and score, stress hormones and ageing markers.
We have also produced the first high-quality reference genome for Asian elephant that is currently being prepared for publication, and genotyped 300 of our study animals.