Jan van Deursen

Rochester, USA

Jan Van Deursen is Vita Valley Professor of Senescence at Mayo Clinic, where he chairs the Department of Biochemistry and Molecular Biology, and Professor of Pediatrics at The Mayo Clinic, Rochester, Minnesota, USA. Dr van Deursen holds a BSc in Biology, MSc in Molecular Biology, and PhD in Cell Biology from the University of Nijmegen, the Netherlands. He is an Honorary Professor at the University of Groningen, the Netherlands and serves on numerous national and international grant review panels. Professor Van Deursen has a longstanding interest in questions related to cell cycle control and cellular responses to stress. He helped establish the concept that, with ageing and development of age-related disease, wasteful transformed cells that cannot divide – “senescent cells”- litter tissues and demonstrated that clearance of these cells extends both health span and lifespan. He established that BubR1 (an essential mitotic checkpoint protein) is causally implicated in cancer and ageing and provided the first in vivo evidence that p16-positive senescent cells drive ageing and age-related disease. Dr Van Deursen has been recognised by numerous awards, and has a strong commitment to supporting the successful careers of young up-and-coming scientists.

Monday 01 June 10:00

Age, the unpreventable risk factor - targeting senescence

Cellular senescence is a process in which cells cease dividing and undergo distinctive phenotypic alterations, including profound chromatin and secretome changes. Senescent cells may only represent 1–5% of the cells in a tissue, but due to their aggressive nature they have a very profound effect on neighbouring cells. Historically, this process has been viewed as an irreversible cell-cycle arrest mechanism that acts to protect against cancer. However, recent insights indicate that, unlike a static endpoint, senescence represents a series of progressive and phenotypically diverse cellular states acquired after the initial growth arrest. Resistance of senescent cells to both extrinsic and intrinsic pro-apoptotic stimuli implies complex regulation of apoptosis. Indeed, this is a highly dynamic, multi-step process, involving morphological changes, chromatin remodelling, and metabolic reprogramming, as well as secretion of a complex mix of mostly proinflammatory factors termed the senescence-associated secretory phenotype. Epigenetic and genetic changes are important in driving these changes. Thus, these findings extend the role of cellular senescence to complex biological processes such as tissue repair, ageing and age-related disorders.

A deeper understanding of the molecular mechanisms underlying the multi-step progression of senescence and the development and function of acute versus chronic senescent cells offers nascent therapeutic potential. Given the heterogeneity of senescent cell phenotypes, characterisation of senescent cells in vivo using single-cell transcriptome and proteome profiling of tissues will be fundamental to this process. Novel senolytic therapies offer possibilities in future regenerative medicine and age-related pathologies.

Key references

van Deursen JM. Senolytic therapies for healthy longevity. Science 2019;364:636-7.

Childs B, van Deursen J. Inhibition of ‘jumping genes’ promotes healthy ageing. Nature 2019;566:46-8.

Childs BG, Li H, van Deursen JM. Senescent cells: a therapeutic target for cardiovascular disease. J Clin Invest 2018;128:1217-28.