A senescent cell bystander effect: senescence‐induced senescence

G Nelson, J Wordsworth, C Wang, D Jurk… - Aging cell, 2012 - Wiley Online Library
Aging cell, 2012Wiley Online Library
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 …
Summary
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.
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