Ageing answers no longer a hard cell

Centenary, Media releases

The holy grail of healthy old age may lie in the riddle of cells that stop Centenary Logocancer and hasten age at the same time.

Professor Judith Campisi, the head of research labs at San Francisco’s Buck Institute for Research on Ageing and the Lawrence Berkeley National Laboratory, will present this research at the Inflammation in Disease and Ageing conference at Manly, organised by the Centenary Institute.

She has found that senescent cells, which stop cancer in its tracks, also promote the inflammation that drives many age-related problems and chronic diseases.

“The good news is that if we can work out a way to maximise the beneficial effects of cell senescence in fighting cancer and wound healing, and minimise the deleterious effects of inflammation in old age, we might reach the Holy Grail of staying healthier for longer,” Professor Campisi says.

“Her work helps us understand the links between inflammation and ageing, which is a key theme of Centenary Institute’s research,” says Professor Jennifer Gamble, one of the conference organisers and the leader of the institute’s Vascular Biology Research Group.


Judith Campisi in Manly

Senescent cells develop as a natural defence to suppress cell growth induced by potentially cancer-inducing stress. The cells stop dividing and can no longer form tumours, but the cells remain alive.

Professor Campisi has found that senescent cells secrete compounds that promote inflammation in the surrounding tissue, a natural part of wound healing.

However, in older people the inflammation can contribute to a range of age-related problems, such as cataracts, chronic diseases and, ironically, late-life cancer.

She has also found that senescent cells accumulate with age in vertebrae tissue and around areas of existing degeneration.

Together with colleagues at the Mayo Clinic, Professor Campisi has shown that eliminating senescent cells in older mice can lead to a healthier, and potentially longer, life.

“Judith Campisi’s research explains why the elderly are at such risk of developing chronic disease,” says Prof Gamble. “It also shows how what happens at the cellular level can have an impact on the whole body. Diabetes, for example, produces a build-up of senescent cells, and that in itself leads to problems with wound healing.

“In my own work, we know that the endothelial cells that form the blood vessels are subject to a lot of stress, induced by such things as changes in blood pressure and diet. My laboratory has already picked up pro-inflammatory senescent cells in endothelial tissue. Interestingly, we have also discovered the first senescent cells which are anti-inflammatory.”

The Manly symposium, organised by the Centenary Institute, is the first of a series of biennial conferences on the Future of Experimental Medicine.

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Background Information

Judith Campisi: presentation abstract

Cellular senescence as a driver of age-related inflammation

Cellular senescence is an established cell fate decision that prevents cancer by suppressing the growth of cells that experience potentially oncogenic stress. These stressors include damage from endogenous and exogenous sources, strong mitogenic stimuli, disruptions to the epigenome, and potentially oncogenic mutations. Senescent cells arrest growth, essentially irreversible, thereby preventing their expansion. In addition, senescent cells adopt a complex program of gene expression, including resistance to apoptotic cell death and development of a complex senescence-associated secretory phenotype (SASP). Among the most highly expressed and secreted SASP factors are numerous pro-inflammatory cytokines. In conjunction with secreted chemokines, growth factors, proteases and other molecules, senescent cells can have potent effects on the tissue microenvironment.

We and others have shown that senescent cells accumulate with age in many vertebrate tissues. They are also present at elevated levels at sites of age-related pathologies, both degenerative and hyperplastic. Thus, whereas the senescence growth arrest is clearly tumor suppressive, the SASP can drive several chronic diseases associated with ageing, including, ironically, cancer ‑ particularly cancer progression to metastasis.

The idea that senescence-derived inflammation can drive ageing and age-related disease is supported by the recent development of mouse models in which senescent cells can be eliminated, and the identification and inhibition of targets in pathways that drive senescence-associated inflammation. The complex nature of cellular senescence and the SASP suggests that tumor suppression by cellular senescence serves multiple purposes, the natures of which depend on age and physiological context. Understanding how this multi-faceted cell fate is regulated has increased our chances of minimizing its deleterious effects, while minimizing its beneficial effects.

About the Future of Experimental Medicine Conference

The Future of Experimental Medicine Conference will be a biennial conference and has been created by the Centenary Institute to build understanding of the impact that researchers and clinicians can have when they work closely together – which is the Centenary model.

The theme of this year’s inaugural Future of Experimental Medicine Conference is Inflammation in Disease and Ageing. We’re only just starting to understand the roles of metabolism, inflammation and ageing in disease and this is a key research direction for Centenary.

The conference will examine frontiers of current basic research and clinical applications, covering topics including immunology, cell migration and signalling, autoimmune diseases, cancer, cardiovascular diseases, allergies and skin diseases.

The inaugural conference is supported by: The Charles Perkins Centre (The University of Sydney), The Ian Potter Foundation, EMBO, AbbVie, Janssen-Cilag, Sydney Medical School, LaVision BioTec, Leica Microsystems, CSL Limited, Business Events NSW, and the NSW Government’s Office for Health and Medical Research.

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About the Centenary Institute

The Centenary Institute is an independent leader in medical research seeking improved treatments and cures for cancer, cardiovascular and infectious diseases. We are working to discover new prevention, early diagnosis and treatment options to enable each generation to live longer, healthier lives than the one before. Centenary’s affiliation with the RPA Hospital and the University of Sydney means that our discoveries can be quickly applied to the fight against disease in the clinic.

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