TY - JOUR
T1 - A senescent cell bystander effect
T2 - Senescence-induced senescence
AU - Nelson, Glyn
AU - Wordsworth, James
AU - Wang, Chunfang
AU - Jurk, Diana
AU - Lawless, Conor
AU - Martin-Ruiz, Carmen
AU - von Zglinicki, Thomas
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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.
KW - 53BP1
KW - Aging
KW - Cell signalling
KW - DNA damage
KW - Fluorescence
KW - GFP
UR - http://www.scopus.com/inward/record.url?scp=84862794254&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862794254&partnerID=8YFLogxK
U2 - 10.1111/j.1474-9726.2012.00795.x
DO - 10.1111/j.1474-9726.2012.00795.x
M3 - Comment/debate
C2 - 22321662
AN - SCOPUS:84862794254
SN - 1474-9718
VL - 11
SP - 345
EP - 349
JO - Aging Cell
JF - Aging Cell
IS - 2
ER -