A senescent cell bystander effect: senescence-induced senescence.
Senescent cells produce and secrete various bioactive molecules including interleukins, growth factors, matrix-degrading enzymes and reactive oxygen species (ROS). Thus, it has been proposed that senescent cells can damage their local environment, and a stimulatory effect on tumour cell growth and invasiveness has been documented. However, it was unknown what effect, if any, senescent cells have on their normal, proliferation-competent counterparts. We show here that senescent cells induce a DNA damage response, characteristic for senescence, in neighbouring cells via gap junction-mediated cell-cell contact and processes involving ROS. Continuous exposure to senescent cells induced cell senescence in intact bystander fibroblasts. Hepatocytes bearing senescence markers clustered together in mice livers. Thus, senescent cells can induce a bystander effect, spreading senescence towards their neighbours in vitro and, possibly, in vivo.
Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, UK.
Glyn
G
Nelson
James
J
Wordsworth
Chunfang
C
Wang
Diana
D
Jurk
Conor
C
Lawless
Carmen
C
Martin-Ruiz
Thomas
T
von Zglinicki
D024201:Bystander Effect; D002460:Cell Line; D016922:Cellular Senescence; D018920:Coculture Techniques; D004249:DNA Damage; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species