A senescent cell bystander effect: senescence-induced senescence

By Glyn Nelson, J. Wordsworth, Chunfang Wang, D. Jurk, Conor Lawless, C. Martin-Ruiz, T. von Zglinicki. Aging Cell, 2012

697 citations recorded by the source corpus.

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.

Subfields: Dermatology, Endocrine and Autonomic Systems, Physiology

View Paper: https://www.semanticscholar.org/paper/11071696f4d62ecff800bdde288c3efbef2509f5

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Dermatology

1. Manuel Serrano
2. M. Blasco
3. P. Jat
4. J. Campisi
5. J. Kirkland
6. J. V. van Deursen
7. R. Kumari
8. T. Tchkonia

In Endocrine and Autonomic Systems

1. Guido Kroemer
2. Linda Partridge
3. J. Campisi

In Physiology

1. J. Kirkland
2. T. Tchkonia
3. J. Campisi
4. Manuel Serrano
5. Guido Kroemer
6. P. Jat
7. R. Kumari
8. M. Blasco

Citations in the corpus

• Inflammaging and 'Garb-aging'. (2017, background): “In favour of this assumption, several data suggest that cell senescence can propagate from cell to cell by a bystander effect (“senescenceinduced senescence”) [66] and transmitted in a paracrine fashion by activation of inflammasome and IL-1 signalling [67].”
• Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal (2014, background): “Mario F. Muñoz was supported by Consejeria de Economı́a, Innovacion y Ciencia de la Junta de Andalucia (Spain) postdoctoral fellowship (P10-CTS-6494).”
• Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021, background): “Induction of p21WAF1/CIP1 is crucial for initiation of senescence mediated growth arrest by different stimuli (Noda et al., 1994; Hernandez-Segura et al., 2017).”
• A proteomic atlas of senescence-associated secretomes for aging biomarker development (2019, background): “senescence [48,49], as well as temporal dynamics of the SASP – all generated by our 373 laboratories.”
• Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines (2018, background): “Senescent cells influence other cells by paracrine and bye-stander effects (114).”
• Mechanisms and functions of cellular senescence. (2018, neutral): “For example, senescent cells can signal and influence adjacent cells through juxtacrine NOTCH/JAG1 signaling (60) or ROS production (61), or by cargo transfer, which occurs via formation of cytoplasmic bridges (62) or release of exosomes (63).”
• Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. (2013, positive): “The SASP also appears to spread from cell to cell (97), potentially amplifying the senescent cell burden, sterile inflammation, and chronic disease progression, especially once the capacity of the immune system to remove senescent cells is overwhelmed.”