Senescence-associated inflammatory responses: aging and cancer perspectives

Lasry, Audrey; Ben‐Neriah, Yinon

doi:10.1016/j.it.2015.02.009

Cited by 344 publications

(254 citation statements)

References 147 publications

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“…Additionally, enhanced inflammatory chemokine/cytokine expression has been shown to be a prominent phenotype in senescent fibroblasts that serve to directly and indirectly (in part through recruitment of tumor promoting immune cells) promote cancer cell growth and survival (Coppe et al ., 2010; Lopez‐Otin et al ., 2013). Other recent studies have emphasized the influence of contexts such as altered tissue microenvironment on age‐dependent incidence of cancers (Lasry & Ben‐Neriah, 2015; Rozhok & DeGregori, 2015). …”

Section: Discussionmentioning

confidence: 99%

Enhanced inflammation and attenuated tumor suppressor pathways are associated with oncogene‐induced lung tumors in aged mice

et al. 2017

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SummaryAging is often accompanied by a dramatic increase in cancer susceptibility. To gain insights into how aging affects tumor susceptibility, we generated a conditional mouse model in which oncogenic Kras G12D was activated specifically in lungs of young (3–5 months) and old (19–24 months) mice. Activation of Kras G12D in old mice resulted in shorter survival and development of higher‐grade lung tumors. Six weeks after Kras G12D activation, old lung tissues contained higher numbers of adenomas than their young tissue counterparts. Lung tumors in old mice displayed higher proliferation rates, as well as attenuated DNA damage and p53 tumor suppressor responses. Gene expression comparison of lung tumors from young and old mice revealed upregulation of extracellular matrix‐related genes in young tumors, indicative of a robust cancer‐associated fibroblast response. In old tumors, numerous inflammation‐related genes such as Ccl7,IL‐1β, Cxcr6, and IL‐15ra were consistently upregulated. Increased numbers of immune cells were localized around the periphery of lung adenomas from old mice. Our experiments indicate that more aggressive lung tumor formation in older Kras G12D mice may be in part the result of subdued tumor suppressor and DNA damage responses, an enhanced inflammatory milieu, and a more accommodating tissue microenvironment.

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Section: Discussionmentioning

confidence: 99%

Enhanced inflammation and attenuated tumor suppressor pathways are associated with oncogene‐induced lung tumors in aged mice

et al. 2017

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“…This response has been termed the "senescence-associated secretory phenotype" or SASP, and its function has been linked to a variety of age-related pathological outcomes, including tumorigenesis and sterile chronic inflammation. 47,48 Recent work has demonstrated that the MRE11 complex and ATM are critical for the innate immune response to cytosolic DNA in bone marrow-derived dendritic cells (BMDCs) 49,50 and in BMDMs. 51 In response to cytosolic DNA generated by increased DNA damage or polyinosinic-polycytidylic acid, BMDCs activate the STING pathway to trigger SASP-inducing inflammatory pathways mediated by IL-1b and the inflammosome.…”

Section: Discussionmentioning

confidence: 99%

NBS1 is required for macrophage homeostasis and functional activity in mice

Pereira-Lopes

Tur

Calatayud-Subias

et al. 2015

Blood

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• Nbs1 is a component of the MRE11 complex, which is a sensor of DNA double-strand breaks and plays a crucial role in the DNA damage response.• In mice with a hypomorphic allele of Nbs1, macrophages exhibit increased senescence and abnormal proliferation and inflammatory responses. , macrophage activation-induced ROS caused increased levels of DNA damage that were associated with defects in proliferation, delayed differentiation, and increased senescence. Furthermore, upon stimulation, Nbs1 ΔB/ΔB macrophages exhibited increased expression of proinflammatory cytokines. In the in vivo 2,4-dinitrofluorobenezene model of inflammation, Nbs1 ΔB/ΔB animals showed increased weight and ear thickness. By using the sterile inflammation by zymosan injection, we found that macrophage proliferation was drastically decreased in the peritoneal cavity of Nbs1 ΔB/ΔB mice. Our findings show that NBS1 is crucial for macrophage function during normal aging. These results have implications for understanding the immune defects observed in patients with NBS and related disorders. (Blood. 2015;126(22):2502-2510

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“…To determine enrichment of cell senescence proteins, a list of SASP proteins were compiled based on prior research (Coppe, Desprez, Krtolica, & Campisi, 2010; Coppe et al., 2008; Lasry & Ben‐Neriah, 2015). There were 72 unique SOMAmer Reagents that recognized proteins previously reported as SASP proteins.…”

Section: Methodsmentioning

confidence: 99%

Plasma proteomic signature of age in healthy humans

Tanaka¹,

Biancotto²,

Moaddel³

et al. 2018

Aging Cell

336

337

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To characterize the proteomic signature of chronological age, 1,301 proteins were measured in plasma using the SOMAscan assay (SomaLogic, Boulder, CO, USA) in a population of 240 healthy men and women, 22–93 years old, who were disease‐ and treatment‐free and had no physical and cognitive impairment. Using a p ≤ 3.83 × 10−5 significance threshold, 197 proteins were positively associated, and 20 proteins were negatively associated with age. Growth differentiation factor 15 (GDF15) had the strongest, positive association with age (GDF15; 0.018 ± 0.001, p = 7.49 × 10−56). In our sample, GDF15 was not associated with other cardiovascular risk factors such as cholesterol or inflammatory markers. The functional pathways enriched in the 217 age‐associated proteins included blood coagulation, chemokine and inflammatory pathways, axon guidance, peptidase activity, and apoptosis. Using elastic net regression models, we created a proteomic signature of age based on relative concentrations of 76 proteins that highly correlated with chronological age (r = 0.94). The generalizability of our findings needs replication in an independent cohort.

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Senescence-associated inflammatory responses: aging and cancer perspectives

Cited by 344 publications

References 147 publications

Enhanced inflammation and attenuated tumor suppressor pathways are associated with oncogene‐induced lung tumors in aged mice

Enhanced inflammation and attenuated tumor suppressor pathways are associated with oncogene‐induced lung tumors in aged mice

NBS1 is required for macrophage homeostasis and functional activity in mice

Plasma proteomic signature of age in healthy humans

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