Cellular senescence in aging and age-related diseases

Cellular senescence, a permanent state of cell cycle arrest accompanied by a complex phenotype, is an essential mechanism that limits tumorigenesis and tissue damage.  In physiological conditions, senescent cells can be removed by the immune system, facilitating tumour suppression, wound healing and possibly embryonic development.  However, as we age, senescent cells appear to accumulate in tissues, either because an aging immune system fails to remove them, the rate of senescent cell formation is elevated or both.  If senescent cells persist and accumulate in tissues, they have the potential to paradoxically promote pathological conditions. 

One of such conditions, Chronic Obstructive Pulmonary Disease (COPD) is characterized by persistent airflow limitation associated with an enhanced chronic inflammatory response.  COPD is currently the fourth leading cause of death in the developed countries.  Aging is one of the major risk factors for COPD. One emerging hypothesis suggests that alveolar- and airway-cell senescence triggered by environmental stress or aging, contributes to the destruction of alveoli. Cellular senescence can limit the proliferative capacity necessary for tissue repair and promote chronic inflammation via the senescence-associated secretory phenotype (SASP), both of which are hallmarks of COPD. We study the role of senescent cells in the pathology of COPD and other age-related diseases using mouse models.

The persistence and accumulation of senescent cells has been shown to potentially play a role in the pathophysiology of ageing and age-related disease.  In fact, various disorders associated with accelerated ageing such as Hutchinson–Gilford progeria and Werner syndrome have been linked with senescent cells.  Therefore, the elimination of senescent cells from tissues has the potential to increase health-span and possibly even lifespan.  For example, it was recently demonstrated that the elimination of p16-expressing cells in a transgenic mouse model delays age-associated disorders.  As such, there are a number of therapeutic avenues of research that have the potential to eliminate senescent cells or prevent their accumulation (Figure 1) (Burton & Krizhanovsky 2014).