Overview
By 2030, nearly one in five people will be over 65—and by 2050, that number will double. This demographic shift poses enormous challenges to healthcare systems like the NHS, as ageing brings about deep molecular and functional changes across the body. The liver, a vital organ central to metabolism and detoxification, is no exception. With age, its regenerative capacity slows, cellular repair weakens, and susceptibility to disease increases. Yet despite the liver’s central role in maintaining health, our understanding of how ageing reshapes its metabolic landscape remains limited.
About this opportunity
This PhD project offers the chance to tackle a fascinating question: How does liver metabolism change with age, and what do these changes mean for healthy human ageing?
Using the transformative Proteomics technologies developed in the Scheltema Lab (https://www.liverpool.ac.uk/centre-for-proteome-research/), this studentship will investigate molecular ageing in unprecedented detail. To establish feasibility, our team—including Co-Investigators Prof. Goldring, Dr. Sison-Young, Prof. Copple, and Prof. Moore—conducted a pilot liver study comparing young and old donors. From over 5,000 proteins quantified, 1,240 showed significant age-related regulation. Of particular interest were metallothioneins—powerful antioxidant proteins like MTA2, MT1F, and MT1L—which were notably altered with age. Because these proteins depend on zinc, their decline may be linked to zinc deficiency, a common feature of ageing that contributes to immune decline. Similarly, enzymes crucial to detoxification and redox balance, such as GGT5, GSTP1, and GSTA1, also shifted with age, suggesting profound dietary and metabolic implications.
Project Aims and Training
This ambitious project has four interconnected aims:
- Comprehensive Training – Full hands-on training in mass spectrometry-based Proteomics, data analysis, and ex vivo liver modelling;
- Large-Scale Proteomics – Quantitative analysis of 300 well-characterised human liver samples across all adult ages;
- Data Integration – Identification of key molecular pathways driving age-dependent changes in liver metabolism;
- Functional Validation – Experimental testing of age-sensitive enzymes using cutting-edge 3D human liver models.
The work will be conducted at Liverpool’s Centre for Proteome Research, a £20 million world-class facility equipped with high-tech equipment like the new Orbitrap Astral Zoom mass spectrometer. Here, the student will generate high-resolution molecular data, supported by an expert multidisciplinary team and world-leading infrastructure in human liver research.
Functional experiments will use 3D liver spheroids and precision-cut slices from donors spanning the full age range, allowing direct validation of proteomic discoveries in living tissue. This powerful integration of Proteomics, nutrition science, and cell biology will uncover how diet and metabolism interact with age to shape liver health.
By joining this project, you’ll gain exceptional experience in human tissue-based research, advanced data analysis, and translational bioscience—skills in high demand across academia and industry. Most importantly, you’ll contribute to a transformative understanding of how we age, helping pave the way toward a healthier, longer-lived population.
Shape the future of healthy ageing—apply now to explore the molecular secrets of the ageing liver.
Further reading
1. J. Siehler, S. Bilekova, P. Albanese, S. Tamara, C. Jain, M. Sterr, S.J. Enos, C. Chen, P. Chapouton, A. Villalba Felipe, F. Ribaudo, Ansarullah, I. Burtscher, T. Kurth, R. Scharfmann, S. Speier, R.A. Scheltema, H. Lickert$; Inceptor binds and directs insulin to lysosomal degradation in β-cells; Nature Metabolism, 2024
2. Y. Chen, J. Gote-Schniering, M. Müller, P. Albanese, A. Jankevics, R.C. Jentzsch, A. Tata, M. Ansari, L. De Sadeleer, L. Yang, L. Heumos, A. Agami, S. Zhou, C.H. Mayr, R. Hatz, C.P. Schneider, J. Behr, A. Hilgendorff, A.O. Yildirim, M. Stoleriu, P. Dorfmüller, F.J. Theis, P.R. Tata, M.D. Luecken, R.A. Scheltema, H.B. Schiller; A spatially resolved extracellular matrix proteome atlas of the distal human lung; European Respiratory Journal, 2023
3. Weaver RJ, Blomme EA, Chadwick AE, Copple IM, Gerets HHJ, Goldring CE, Guillouzo A, Hewitt PG, Ingelman-Sundberg M, Jensen KG, Juhila S, Klingmüller U, Labbe G, Liguori MJ, Lovatt CA, Morgan P, Naisbitt DJ, Pieters RHH, Snoeys J, van de Water B, Williams DP, Park BK. Managing the challenge of drug-induced liver injury: a roadmap for the development and deployment of preclinical predictive models. Nat Rev Drug Discov. 2020 Feb;19(2):131-148.
4. Bell CC, Hendriks DF, Moro SM, Ellis E, Walsh J, Renblom A, Fredriksson Puigvert L, Dankers AC, Jacobs F, Snoeys J, Sison-Young RL, Jenkins RE, Nordling Å, Mkrtchian S, Park BK, Kitteringham NR, Goldring CE, Lauschke VM, Ingelman-Sundberg M. Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease. Sci Rep. 2016 May 4;6:25187.
5. Livoti LA, Sison-Young R, Reddyhoff D, Fisher CP, Gardner I, Diaz-Nieto R, Goldring CE, Copple IM (2025) Limitations of acetaminophen as a reference hepatotoxin for the evaluation of in vitro liver models, Toxicol Sci, 203, 35-40.