[Plenary] Judith Campisi: Puzzles and Promises of Cellular Senescence
Judith Campisi, PhD
Lawrence Berkeley National Laboratory, CA, USA
Cellular senescence is a complex cell fate that leads to a tripartite phenotype: an essentially irreversible arrest of cell proliferation; a multi-faceted secretory phenotype; and relative resistance to apoptosis. The senescent state is induced by both stressful and physiological stimuli. The growth arrest is known to be a potent tumor suppressive mechanism, whereas the resistance to apoptosis is thought to partly explain why senescent cells increase with age. The senescence-associated secretory phenotype (SASP) is thought to drive many of the beneficial (e.g., pro-wound healing) of senescent cells, as well as many of their deleterious effects (e.g., pro-aging phenotypes and age-related pathologies). Both effects may be due to pro-inflammatory nature of the SASP. Transgenic mouse models in which senescent cells can be selectively eliminated have established that senescent cells are indeed causal for a growing number of aging phenotypes and diseases. Thus, clearing senescent cells can prevent, ameliorate or, in some cases, reverse the deleterious effects of senescent cells. These findings have led to a surge in the search for small molecules that can mimic the mouse transgenes. Indeed, several such ‘senolytics’ have now been identified. While these drugs hold promise for improving health in humans, they also reveal unexplained complexities in the senescence response. The composition of the SASP, for example, depends on the cell type, inducer and timing. In addition, senescent cells are surprisingly heterogeneous, even when controlling for genotype, cell type and inducer. It is not clear which senescent subtypes senolytics target, nor which subtypes should be targeted. Thus, the field is at an early stage. Nonetheless, the idea that senescent cells can drive multiple age-related pathologies is gaining traction, and this idea opens new possibilities for extending the health span of humans.
Dr. Campisi received a PhD in biochemistry from the State University of New York at Stony Brook and completed her postdoctoral training at the Dana‐Farber Cancer Institute and Harvard Medical School. As an associate professor at the Boston University Medical School, she studied the role of cellular senescence in suppressing cancer and soon became convinced that senescent cells also contributed to aging. She joined the Lawrence Berkeley National Laboratory as a senior scientist in 1991. In 2002, she started a laboratory at the Buck Institute. Dr. Campisi has established a broad program to understand the relationship between aging and age‐related disease, with an emphasis on the interface between cancer and aging.
Dr. Campisi is a member of the National Academy of Sciences and a fellow of the American Association for the Advancement of Science.
She has received numerous awards for her research, including two MERIT awards from the National Institute on Aging and awards from the AlliedSignal Corporation, Gerontological Society of America, and American Federation for Aging Research. She is a recipient of the Longevity prize from the IPSEN Foundation, the Bennett Cohen award from the University of Michigan, and the Schober award from Halle University, and she is the first recipient of the international Olav Thon Foundation prize in Natural Sciences and Medicine. Dr. Campisi is an editorial board member for more than a dozen peer‐reviewed journals. She is a scientific co‐ founder of Unity Biotechnology, a California‐based company focused on developing therapies for age‐related pathologies.
Host: Carolina Florian