Periodic Reporting for period 1 - GAE (Genomics of Ageing in Elephants: Genomic architecture of senescence in a long-lived mammal)
Période du rapport: 2018-06-01 au 2020-05-31
"European populations are ageing, and this has important health, economic and social consequences. Yet in order to manage these, we need to understand the complex phenomenon of ""biological age"", and in particular its genetic determinants. It is now established that longevity insurance genes such as TP53 mitigate the roles of mitochondrial function, oxidative stress and telomere shortening, and that these genes are also involved in ageing, with senescence and cancer being two faces of the cell growth balance. Thus, longevity is a trade-off between cancer and ageing, but also possibly fertility and menopause. In that respect, Asian elephants are a fascinating model: similar to humans in lifespan, senescence, they are almost exempt of cancer, contrary to predictions based on their large size. Recently, multiple retrocopies of TP53 have been identified in elephants: a strong argument to consider that cancer- avoidance and a long lifespan are the product of genetic adaptations in proboscideans. The genetic architecture of human- like ageing is impossible to study in classical short-lived models, as they lack the traits that make human life-history special, like a post-reproductive lifespan. This Action endeavoured to bring together a large life-history and health dataset and extensive genomic data on the Asian elephant to shed light on this particular system. During this action the basis for a draft reference genome for the Asian elephant was established, that future studies into genomics of ageing will build on."
Work performed during the project focused on creating a reference genome for the Asian elephant. With the aid of the host genetic resources and financial support, high-coverage data on Asian elephant genome was produced using a variety of approaches. Altogether, we analysed 10X linked-reads at a depth of ~50X, PacBio long reads at a depth of ~13X and Oxford Nanopore long reads at a depth of ~2X. These data form a basis for an annotated whole-genome assembly that can be used in future studies into genomics of ageing. The researcher was also involved in collaborative research that produced a comprehensive assessment of health in this long-lived species. Two manuscripts from this work are currently under review, showing that (1) The biggest annual differences in health of the study elephants occurred between the hot and monsoon seasons, including changes in haematological, immunological, muscular, kidney and liver functions, as well as protein balance and electrolytes and that (2) Heavily parasitized individuals showed the poorest health, most strongly evident in our immune measures. Further collaborative work exploring the link between lifespan and senescence in humans, comparing the patterns of both survival and reproductive senescence in short- and long-lived individuals, is currently prepared for publication. The results have been actively disseminated to stakeholders in Myanmar.
Training during this Action led to the researcher obtaining highly esteemed Academy of Finland fellowship for 2020-23 to continue the goals of GAE as an independent research fellow at the University of Turku. The work carried out in the Action also has practical value, given that elephant welfare remains a central stake for the sustainable development of the Burmese forest economy. The important welfare (e.g. senescence-related) and conservation goals of this project have therefore been directly communicated to the stakeholders in Myanmar.