Oral Presentation 26th Lorne Cancer Conference 2014

Cancer, aging and cellular senescence: Jekyll AND Hyde (#24)

Judy Campisi 1
  1. Buck Institute for Research on Aging and Lawrence Berkeley National Laboratory,

Cellular senescence is an established mechanism for preventing cancer by preventing the growth of cell that experience potentially oncogenic stress.  In addition to arresting growth – essentially irreversibly – senescent cells also adopt a complex program of gene expression termed the senescence-associated secretory phenotype (SASP).  Among the most highly expressed and secreted SASP factors are numerous pro-inflammatory cytokines.  However, SASP factors also include secreted chemokines, growth factors, proteases and other molecules that can have potent effects on the tissue microenvironment.  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.  The senescence growth arrest is clearly tumor suppressive.  However, the SASP can drive several chronic diseases associated with aging, including, ironically, cancer – particularly cancer progression to metastasis.  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 increase our chances of minimizing its deleterious effects, while minimizing its beneficial effects, including its ability to limit cancer progression.