Projects per year
My work centres on the mechanisms and consequences of cellular senescence. Senescent cells are the living, but permanently non-dividing, forms of cells which are normally capable of division within mammalian tissues. Thus it is possible to have both growing and senescent forms of fibroblasts, keratinocytes, astrocytes, endothelial cells, vascular smooth muscle cells but not neurons or red blood cells. The senescent state is distinct from quiescence (transient growth arrest induced by contact inhibition or serum withdrawal), from cell death (senescent cells remain viable for many years) and from terminal differentiation. In vivo senescence primarily exists to limit the capacity for expansion of clones of cells and thus limit the opportunities for them to accumulate pro-carcinogenic mutations. When senescence was first observed in vitro in the early 1960s Leonard Hayflick proposed that the phenomenon was related to ageing. Although this theory was bitterly contested for decades it is now clear that the progressive accumulation of senescent cells is a major cause of ageing in mammals. I study three distinct aspects of this process.
 Senescence as a cause of human ageing: Perhaps the best evidence for the role of senescence in human ageing is provided by the genetic disease Werner’s syndrome (WS). This is caused by loss of function mutations in the RecQ helicase and individuals prematurely display features of premature ageing in many but not all tissues. My doctoral work demonstrated that WS fibroblasts showed intrinsically accelerated rates of senescence compared to those from normal donors. Further BBSRC supported research found that cell types derived from prematurely aged WS tissues show accelerated senescence, whilst tissues from the same patients that age normally do not. This demonstrates both that senescent cells can cause ageing in humans and that WS is not simply a global 'DNA damage syndrome' caused by loss of RecQ.
 The phenotype of senescent cells: Further support from the BBSRC allowed the analysis of the senescent phenotype and mechanisms controlling entry into the senescent state in multiple different human cell types. Genomic analysis revealed that senescent vascular smooth muscle cells exhibited a pro-calcificatory phenotype and that senescent keratocytes do not display a senescence associated secretory phenotype (SASP). Novel mechanisms controlling senescence in the human corneal endothelium were also discovered.
 The reversal of senescence and its effects: Building on these findings further awards allowed the study of novel compounds (SB203580, UR-13756 and BIRB 796) that inhibit senescence and the SASP via the p38 MAPK pathway. We have also developed a novel synthetic route for, and library of, polyphenolics based on a resveratrol backbone. These have the remarkable property of rescuing multiple types of previously senescent cells- opening up entirely new potential ways in which to treat age-related disorders. We are now actively investigating the therapeutic potential of these compounds in both bioartificial organs and for the treatment of therapy induced senescence.
I am past Chair of the British Society for Research on Ageing, the International Association of Biomedical Gerontology and the American Aging Association. I read Biochemistry at Imperial College, London and undertook doctoral studies at the University of Sussex. I have served on grant awarding panels for major charities both here and in the United States as well as strategy and funding panels for the BBSRC, the US National Institutes on Ageing and the European Union. I am a member of the Board of Directors of the American Federation for Aging Research (AFAR) and a Trustee of the Biogerontology Research Foundation. I currently serve as a member of the Scientific Advisory Board of the Longevity Vision Fund- an investment Trust which seeks to support early stage companies whose mission is to improve healthy human longevity.
I have received the Royal Pharmaceutical Society Conference Science Medal for outstanding scientific achievement, the Paul F Glenn Award for research into the biological mechanisms of the ageing process and the Lord Cohen Medal for services to gerontology. I have also been honoured by Help the Aged for my championship of older people and the use of research for their benefit.
Approach to teaching
I do not teach. I lecture. I introduce new undergraduates to classical genetics, evolution and molecular biology. At higher levels I explain the fundamental mechanisms of ageing and supervise project students. I continue this research theme with Masters students and also discuss the cognitive basis of scientific controversies. I run intensive, week long, laboratory workshops covering basic molecular biology techniques and explore critical thinking and scientific publication with doctoral students from across the University. I believe a sound understanding of science is important to the cultivation of the entire person, regardless of their primary discipline.
My approach is underpinned by Dwek’s discovery of the relationship between enhanced student success, high perceived self-efficacy and a self-conception of intelligence as fluid. This relationship is rooted in biological reality- perhaps best evidenced by the “Wilson effect” (the increase in broad heritability of intelligence with increasing age). Where apropriate I explore the genetics of open mindsets and IQ to reinforce both subject knowledge and enhance self-efficacy in individual learners.
I apply the latest research on the neuroscience of learning to the design of my modules which currently incorporate the following cognitive principles:
 Content is arranged to form a coherent narrative arc broken up with dedicated formative activity sessions and the opportunity to revisit material covered in earlier lectures in later ones.
For example, when studying evolution and genetics I treat the period 1860-2018 as a historical story arc to exploit the cognitive observation that stories are “cognitively privileged” and treated preferentially in memory. After each lecture block there are formative sessions incorporating both multiple choice and short answer questions to facilitate cognitive “deep transfer” of abstract concepts and prepare students for examinations. This approach is sometimes described as “constructive alignment”.
 Lecture content is arranged such that each lecture highlights conflicting experiments and models rather than simply ‘listing facts’. Structuring learning around a conflict or a larger question and its resolution is a highly effective way of engaging students with the scientific discovery process.
 Modules at higher levels explicitly key into earlier learning. This is based on (a) the evidence that learning occurs through the relation of new information to prior knowledge and concepts in long term memory and (b) that spaced practice shows a strong protective effect against forgetting both in the exam room and in the real world. Like Socrates I believe 'the unexamined life is not worth living'. Unlike him, I consider traditional examinations to be the best tool to assess the academic capacities of every student.
I have supervised students in the areas of cellular senescence (looking at multiple cell types including T cells and vascular smooth muscle cells), ocular wound healing, genomics, synthetic chemistry and the inflammatory response to biomaterials. I have also supervised students studying the accelerated ageing disease Werner's syndrome. This is my academic first love.
My students have won medals for the quality of their theses and gone on to post doctoral positions in chemistry and life science departments in the United States as well as research institutes in Israel. They hold senior academic positions at Universities and have been prestigious Marie Curie Fellows. They have also enjoyed success in scientific publishing.
I am currently supervising work on the impact of senescence on the performance of bioartificial livers with a view to using the novel anti-senescence compounds we have developed to enhance the efficiency of these devices and keep patients alive and healthy until a suitable transplant donor can be found.
I am happy to discuss these or any related research areas.
PhD, University of Sussex
Award Date: 1 Jan 1994
Bachelor, Imperial College London
1 Oct 1986 → 30 Jun 1989
Research Output per year
Novel resveratrol derivatives have diverse effects on the survival, proliferation and senescence of primary human fibroblastsBirar, V. C., Sheerin, A. N., Ostler, E. L. & Faragher, R. G. A., 13 Aug 2020, In : Biogerontology.
Research output: Contribution to journal › Article
Research output: Contribution to journal › Literature review
FOXO1 and ETV6 genes may represent novel regulators of splicing factor expression in cellular senescenceLatorre, E., Ostler, E. L., Faragher, R. G. A. & Harries, L. W., 8 Aug 2018, In : The FASEB Journal.
Research output: Contribution to journal › Article