Background: There is tremendous variation in the rate of senescence – the deterioration of physiological performance with age – both between and within species. For example, mammals show 100-fold variation in lifespan, and it remains a mystery why closely related species of similar size and physiology age at such different rates(1). Individuals from the same species, including humans, also present considerable variation in ageing rate, and this too is not yet fully explained(2). This project aims to explain variation in ageing rate that is due to environmental stress. For this, we use the wood mouse, a powerful experimental, but wild, mammalian system where we can study epigenetic and lifespan variation. The wood mouse is very closely related to the mice we use in laboratories, but in many respects mirrors human lives better than laboratory mice. With wood mice we have a powerful system to enquire about the ageing effects of living in the wild, infection, multiple infections, immune status and history, anti-parasite treatment and nutrition.
The project will specifically consider the hypothesis that variation in longevity and ageing is related to, and even regulated by, DNA methylation. This is not conjectural: DNA methylation plays a role in most developmental and cellular processes, and methylation is tightly associated with age-related diseases. Indeed, with age, the amount of methylation at many genomic sites changes in a clock-like fashion, such that methylation-based epigenetic clocks are highly accurate age estimators (3)(4). In humans, epigenetic clocks are a strong predictor of all-cause mortality, with ticking rates associated with intrinsic developmental processes (presumably under genetic control, i.e., programmed), and responses to environmental stressors (i.e., lifestyle and immune responses)(3). Thus, progress in methylation research neatly bridges genetics to the environment and disease(5). The existence of common genetic and environmental drivers of epigenetic change suggests the possibility of general anti-ageing interventions.
Training outcomes: The student will become an expert in DNA extraction and sequencing, bioinformatics, advanced statistics, and epigenetics. Depending on the interests of the student, the project can also develop parasitological or immunological assays to understand the relationship between immune status and biological age.
The “Visit Website” button will take you to our Online Application checklist. Complete each step and download the checklist which will provide a list of funding options and guide you through the application process. Follow the instructions on the EASTBIO website (you will be directed here from our application checklist), ensuring you upload an EASTBIO application form and transcripts to your application, and ticking the box to request references. Your referees should upload their references using the EASTBIO reference form, in time for the 5th January deadline so please give them plenty of time to do this by applying early.
1. R. Tacutu, T. Craig, A. Budovsky, D. Wuttke, G. Lehmann, D. Taranukha, J. Costa, V. E. Fraifeld, J. P. de Magalhães, Human Ageing Genomic Resources: Integrated databases and tools for the biology and genetics of ageing. Nucleic Acids Research. 41, D1027–D1033 (2012).
2. P. R. Timmers, N. Mounier, K. Lall, K. Fischer, Z. Ning, X. Feng, A. D. Bretherick, D. W. Clark, eQTLGen Consortium, X. Shen, T. Esko, Z. Kutalik, J. F. Wilson, P. K. Joshi, Genomics of 1 million parent lifespans implicates novel pathways and common diseases and distinguishes survival chances. eLife. 8, e39856 (2019).
3. S. Horvath, K. Raj, DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nature Reviews Genetics. 19, 371–384 (2018).
4. J. Jylhävä, N. L. Pedersen, S. Hägg, Biological Age Predictors. EBioMedicine. 21, 29–36 (2017).
5. G. Cavalli, E. Heard, Advances in epigenetics link genetics to the environment and disease. Nature. 571, 489–499 (2019).
How good is research at University of Edinburgh in Biological Sciences?
FTE Category A staff submitted: 109.70
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