Senescence-associated secretory phenotype


Senescence-associated secretory phenotype is a phenotype associated with senescent cells wherein those cells secrete high levels of inflammatory cytokines, immune modulators, growth factors, and proteases. SASP may also consist of exosomes and ectosomes containing enzymes, microRNA, DNA fragments, and other bioactive factors. SASP is heterogenous, with the exact composition dependent upon the senescent-cell inducer and the cell type. Initially, SASP is immunosuppressive and profibrotic, but progresses to become proinflammatory and.
An online serves as a guide to the various types of SASP.
SASP is one of the three main features of senescent cells, the other two features being arrested cell growth, and resistance to apoptosis.

Causes

SASP expression is induced by a number of transcription factors, including C/EBPβ, of which the most important is NF-κB. NF-κB is expressed as a result of inhibition of autophagy-mediated degradation of the transcription factor GATA4. GATA4 is activated by the DNA damage response factors, which induce cellular senescence.

Pathology

SASP factors induce insulin resistance.
SASP disrupts normal tissue function by producing chronic inflammation, induction of fibrosis and inhibition of stem cells. Chronic inflammation associated with aging has been termed inflammaging, although SASP may be only one of the possible causes of this condition. SASP factors stimulate the immune system to eliminate senescent cells.
SASP factors from senescent cells reduce nicotinamide adenine dinucleotide in non-senescent cells, thereby reducing the capacity for DNA repair and sirtuin activity in non-senescent cells.
Despite the fact that cellular senescence likely evolved as a means of protecting against cancer early in life, SASP promotes the development of late-life cancers. Cancer invasiveness is promoted primarily though the actions of the SASP factors interleukin 6 and interleukin 8. In fact, SASP from senescent cells is associated with many aging-associated diseases, including not only cancer, but atherosclerosis and osteoarthritis. For this reason, senolytic therapy has been proposed as a generalized treatment for these and many other diseases.

Benefits

SASP can aid in signaling to immune cells for senescent cell clearance, with specific SASP
factors secreted by senescent cells attracting and activating different components of both the innate and adaptive immune system. But with chronic inflammation, immune system function may be suppressed.
SASP can also play a beneficial role by promoting wound healing. However, in contrast to the persistent character of SASP in chronic inflammation, beneficial SASP in wound healing is transitory.
SASP may also play a role in tissue regeneration by signaling for senescent cell clearance by immune cells, allowing progenitor cells to repopulate tissue. In development, SASP also may be used to signal for senescent cell clearance to aid tissue remodeling.

History

The concept and abbreviation of SASP was first established by Judith Campisi and her group, who first published on the subject in 2008.