Ageing liver and metabolic fatty liver diseases

Chronological ageing is an established risk factor for metabolic and viral related end stage liver diseases. The progression to cirrhosis is the most common indication for liver transplantation. The high incidence of fatty liver disease (~30% of global population) means that there is an ever-increasing need for liver transplantation. An informed approach to reverse ageing requires understanding biological ageing (e.g., a 60-year-old person with advanced fatty liver could have a liver that is 90 years old in biological age). In addition, the scale of biological networks derangement in end stage liver diseases is incongruent with the traditional approaches to medicine. Therefore, we use systems medicine, and disease modeling to design complex therapies to reverse an aged and dysfunctional liver. Identifying the perturbed biological networks at the cellular level, and correcting their functions through a modular approach, constitutes our rationale for multi-stage and complex gene therapies. We will measure the degree of derangement in biological networks and their correction in response to therapies to reinstate liver homeostasis.

Recent Achievements

  • Characterizing liver ageing networks in pre-clinical models
  • Identifying liver-bone marrow cross-talk through bile acids

Recent publications

Core liver homeostatic co-expression networks are preserved but respond to perturbations in an organism- and disease-specific manner. Cell Systems. 2021 Apr 29:S2405-4712(21)00113-7. Doi: 10.1016/j.cels.2021.04.004.

April 2021

Bile acids mediate liver-bone marrow crosstalk. bioRxiv 2023.07.05.546968; doi: https://doi.org/10.1101/2023.07.05.546968

July 2023

Bone marrow haematopoietic stem cells influence liver homeostatic networks and cancer development after dietary intervention. bioRxiv 2022.04.16.488543; https://doi.org/10.1101/2022.04.16.488543

April 2022

Lean NAFLD: A Distinct Entity Shaped by Differential Metabolic Adaptation. Hepatology. 2020 Apr;71(4):1213-1227. doi: 10.1002/hep.30908. Epub 2020 Jan 24.PMID: 31442319

January 2020

NAME ROLE
Prof. Jacob George Director, Storr liver centre
Dr Saeed Esmaili Group Leader
Mr Maito Suo PhD student

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