Targeting ageing: Genes and compounds with pro-longevity, health-preserving effects

Description

Ageing is arguably the major biomedical challenge of the 21st century. In model organisms, the process of ageing can be manipulated by both genetic manipulations and dietary interventions. Although many genes have already been associated with longevity in model systems, which are the most promising for targeting ageing remain unknown and identifying new powerful targets for preserving health in old age would have widespread applications. Likewise, although a few compounds with possible pro-longevity effects are undergoing clinical trials, discovering new compounds that protect against ageing and promote longevity and health in old age is of great importance.

In this project, we aim to identify new genes and compounds with pro-longevity, health-promoting effects. To achieve this, we have already performed sophisticated bioinformatics ad machine learning analyses for prioritizing candidates and demonstrated in model organisms that our predictions yield biologically-relevant results. Therefore, our prioritized candidates for pro-longevity effects will allow us to focus on a relatively small number of high-confidence targets and compounds. These will be studied in well-established worm models for effects on longevity. Besides, healthspan assays will be conducted to determine whether promising drugs improve health in addition to lifespan. Mechanisms of action will also be explored by testing longevity effects in known ageing-related mutants and by employing standard biochemical and molecular techniques. Furthermore, studies in mammalian cells will be performed to assay for potential effects relevant to humans. Specifically, models of induced senescence will be employed to assay for protective roles of genes and drugs. The exact direction of this project and methods to be used, however, will be adapted to fit the research interests and background of the student.

Pro-longevity drugs are already being clinically explored with ongoing clinical trials for several age-related diseases like cancer and type 2 diabetes. This project will provide new pro-longevity genes and compounds which will open translational opportunities to develop human therapies targeting age-related conditions.

Further details about our work on aging and age-related diseases are available at:

https://www.liverpool.ac.uk/ageing-and-chronic-disease/staff/joao-de-magalhaes/

Potential applicants are encouraged to contact Professor de Magalhaes () in the first instance for an informal discussion.

Training:

This project will provide a rich and diverse training in contemporary methods in genetics of model organisms, pharmacology, biochemistry and cell and molecular biology techniques applied to ageing research and dietary manipulations of ageing in particular.

In addition to the generic skills training that is provided through the Institute and University PhD programme, the student will be supported by an excellent infrastructure and will work closely with experts on the biology and genetics of ageing, model organisms, pharmacology, nutrition, and cell and molecular biology. This diverse and stimulating environment will allow a creative and talented student to develop key skills and the project is flexible enough to allow the student to develop his or her own research interests. The student will be well-prepared for a successful career in research and in biotechnology.

Availability

Open to students worldwide

Funding information

Self-funded project

This project is open to applicants who are able to obtain their own funding. We have a thriving international researcher community and encourage applications from students of any nationality able to fund their own studies or who wish to apply for their own funding.

Supervisors

References

Avelar RA, Ortega JG, Tacutu R, Tyler E, Bennett D, Binetti P, Budovsky A, Chatsirisupachai K, Johnson E, Murray A, Shields S, Tejada-Martinez D, Thornton D, Fraifeld VE, Bishop C, de Magalhães JP (2020) "A multidimensional systems biology analysis of cellular senescence in ageing and disease." Genome Biology 21:91.
Calimport SRG, Bentley BL, Stewart CE, Pawelec G, Scuteri A, Vinciguerra M, Slack C, Chen D, Harries LW, Marchant G, Fleming GA, Conboy M, Antebi A, Small GW, Gil J, Lakatta EG, Richardson A, Rosen C, Nikolich K, Wyss-Coray T, Steinman L, Montine T, de Magalhães JP, Campisi J, Church G (2019) "To help aging populations, classify organismal senescence." Science 366:576-578.
Fabris F, Palmer D, Salama KM, de Magalhães JP, Freitas AA (2020) "Using deep learning to associate human genes with age-related diseases." Bioinformatics 36:2202-2208.
Calvert S, Tacutu R, Teixeira R, Ghosh P, de Magalhães JP (2016) “A network pharmacology approach reveals new candidate caloric restriction mimetics in C. elegans.” Aging Cell 15:256-266.
For full list of publications see:
http://pcwww.liv.ac.uk/~aging/publications.html
Further details about our lab are available at:
http://pcwww.liv.ac.uk/~aging/