Inflammatory Networks during Cellular Senescence: Causes and Consequences

By Adam Freund, Arturo V. Orjalo, P. Desprez, J. Campisi. Trends in Molecular Medicine, 2010

1,311 citations recorded by the source corpus.

Chronic inflammation is associated with aging and plays a causative role in several age-related diseases such as cancer, atherosclerosis and osteoarthritis. The source of this chronic inflammation is often attributed to the progressive activation of immune cells over time. However, recent studies have shown that the process of cellular senescence, a tumor suppressive stress response that is also associated with aging, entails a striking increase in the secretion of pro-inflammatory proteins and might be an important additional contributor to chronic inflammation. Here, we list the secreted factors that make up the pro-inflammatory phenotype of senescent cells and describe the impact of these factors on tissue homeostasis. We also summarize the cellular pathways/processes that are known to regulate this phenotype – namely, the DNA damage response, microRNAs, key transcription factors and kinases and chromatin remodeling.

Subfields: Immunology, Physiology

View Paper: https://www.semanticscholar.org/paper/8123cb6b710081dd80220a3cd9089f7301c783df

How researchers see this paper

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

In Immunology

1. J. Campisi
2. J. Kirkland
3. T. Tchkonia
4. M. Demaria
5. Adam Freund
6. J. V. van Deursen
7. Yi Zhu
8. C. Patil

In Physiology

1. J. Campisi
2. M. Demaria
3. J. Kirkland
4. T. Tchkonia
5. Adam Freund
6. F. Rodier
7. Rémi-Martin Laberge
8. J. V. van Deursen

Citations in the corpus

• Aging, Cellular Senescence, and Cancer (2012, background): “Finally, the SASP also includes proteins that can help senescent cells evade immune recognition and clearance (92, 93).”
• p38MAPK is a novel DNA damage response‐independent regulator of the senescence‐associated secretory phenotype (2011, background): “…of the lowaffinity sites, making both p38MAPK and the DDR necessary for NF-kB activity. p38MAPK was crucial for the expression of many SASP cytokines and chemokines, which are largely pro-inflammatory and pro-carcinogenic (Davalos et al, 2010; Freund et al, 2010; Coppe et al, 2010a).”
• Control of the senescence-associated secretory phenotype by NF-κB promotes senescence and enhances chemosensitivity. (2011, result): “Consistent with our results, NF-kB is also activated and contributes to cell cycle arrest in immortalized epithelial cells following withdrawal of SV40 T antigen (Hardy et al. 2005; Rovillain et al. 2011).”
• Programmed cell senescence during mammalian embryonic development. (2013, neutral): “…secretory phenotype (SASP) can also evoke a local inflammatory response with complex effects, including the elimination of senescent cells by phagocytosis, thus leading to tissue remodeling and damage resolution (Freund et al., 2010; Hoenicke and Zender, 2012; Krizhanovsky et al., 2008).”
• Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. (2013, neutral): “61–64 , 92– 94 ).”
• Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines (2018, background): “Therapeutic opportunities may arise through better understanding of the molecular mechanisms that induce senescent cells and SASP in the cellular environments of chronic disease or whether senescent cells can be removed by upregulating autophagy and using sophisticated tagging mechanisms (110).”
• Senescence is a developmental mechanism that contributes to embryonic growth and patterning. (2013, background): “This secretome is largely composed of growth factors, cytokines/chemokines, and extracellular-matrix-remodeling proteins secreted by the arrested cells (Freund et al., 2010).”
• Four faces of cellular senescence (2011, neutral): “, 2009), which are required for the expression of many SASP proteins (Fig. 3; Acosta et al., 2008; Kuilman et al., 2008; Freund et al., 2010).”
• Mechanisms and Metabolic Implications of Regional Differences among Fat Depots (2013, background): “Senescent cells release proinflammatory cytokines, chemokines, and extracellular matrix proteases, termed the senescence-associated secretory phenotype, or SASP (reviewed in Freund et al., 2010).”
• An Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA. (2026, background): “It remains unclear why senescent cells express a SASP given its prominent inflammatory components and mostly detrimental consequences (Freund et al., 2010).”