Age-Associated Increase in Cytokine Production During Systemic Inflammation—II: The Role of IL-1β in Age-Dependent IL-6 Upregulation in Adipose Tissue

Starr, Marlene E.; Saito, Mizuki; Evers, B. Mark; Saitō, Hiroshi

doi:10.1093/gerona/glu197

Cited by 73 publications

(56 citation statements)

References 49 publications

(52 reference statements)

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“…Evidence in vitro suggests that two key mechanisms are likely at play in senescence-driven tissue dysfunction, namely deterioration of tissue maintenance processes due to the SASP and removal of reparative stem and progenitor cells from the proliferative pool through senescence itself. Support for this two-part model includes the presence of SASP factors, as described in vitro , that are known to have in vivo functions in aging, such as the cytokines IL-6 and TNFα in aging tissues 70,71 .…”

Section: Senescence In Normal Agingmentioning

confidence: 99%

Cellular senescence in aging and age-related disease: from mechanisms to therapy

Childs

Durik

Baker

et al. 2015

Nat Med

1,756

1,489

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Cellular senescence, a process that imposes permanent proliferative arrest on cells in response to various stressors, has emerged as a potentially important contributor to aging and age-related disease, and it is an attractive target for therapeutic exploitation. A wealth of information about senescence in cultured cells has been acquired over the past half century; however, senescence in living organisms is poorly understood, largely because of technical limitations relating to the identification and characterization of senescent cells in tissues and organs. Furthermore, newly recognized beneficial signaling functions of senescence suggest that indiscriminately targeting senescent cells or modulating their secretome for anti-aging therapy may have negative consequences. Here we discuss current progress and challenges in understanding the stressors that induce senescence in vivo, the cell types that are prone to senesce, and the autocrine and paracrine properties of senescent cells in the contexts of aging and age-related diseases as well as disease therapy.

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Section: Senescence In Normal Agingmentioning

confidence: 99%

Cellular senescence in aging and age-related disease: from mechanisms to therapy

Childs

Durik

Baker

et al. 2015

Nat Med

1,756

1,489

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“…The IL-6 signaling pathway has been reported to be upregulated in adipose tissue in response to LPS, 34 therefore we assessed the mRNA expression of IL-6 and SOCS3, along with the phosphorylation of STAT3 (downstream effector of IL-6 signaling). LPS induced increases in all indices of IL-6 signaling in both iWAT and eWAT.…”

Section: Vwr Attenuates Body Mass Gain Improves Glucose Tolerance Amentioning

confidence: 99%

Habitual physical activity protects against lipopolysaccharide-induced inflammation in mouse adipose tissue

et al. 2016

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Sepsis is a systemic inflammatory response to infection, with no preventative strategies. In this study, we identify a role for habitual physical activity in the prevention of adipose tissue inflammation induced by a model of sepsis, lipopolysaccharide (LPS). Male C57BL/6J mice (8 weeks old) were housed with access to voluntary wheel running (VWR) or sedentary (SED) for 10 weeks. Mice were then injected with LPS (2 mg/kg) or saline (SAL), and tissues were removed 6 hours postinjection. VWR attenuated body, epididymal adipose tissue (eWAT), and subcutaneous inguinal adipose tissue (iWAT) mass gain, improved glucose tolerance, increased markers of mitochondrial biogenesis in iWAT and eWAT, and increased UCP-1 protein content in iWAT. In iWAT, VWR attenuated the LPS induced increase in mRNA expression of TNF-a, MCP-1, and follistatin, along with phosphorylation of STAT3. In addition, VWR had a main effect for reducing iWAT mRNA expression of IL-1b, IL-6, and SOCS3. In eWAT, VWR had a main effect for reducing mRNA expression of IL-1b, MCP-1, IL-6, and follistatin. Further, VWR increased SOCS3 mRNA expression and phosphorylation of STAT3 in SAL mice, thus the relative change in response to LPS for these markers was attenuated. The protective effect of prior physical activity occurred in conjunction with increases in the protein content of a component of the LPS binding complex, MyD88. Overall, the results from this study demonstrate that habitual physical activity can attenuate the LPS induced inflammatory response in adipose tissue and this occurs to a greater extent in iWAT compare with eWAT.

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“…Most notably, its ability to produce and secrete a variety of inflammatory cytokines and hormones, and its multiple anatomical locations within the viscera contribute to this reputation (24-27). In addition to location, there are multiple suggestions that it is the quality of the adipose tissue rather than the quantity which contributes most to adipose tissue hyper-inflammation or dysfunction (11, 12, 28-31). For example, in our recent study using explant cultures of adipose tissue from young (4-month) and aged (24-month) mice, LPS treatment induced a stronger inflammatory response in tissues taken from aged mice, indicating that aged fat, regardless of quantity or systemic contribution from the aging body, is prone to an exaggerated inflammatory response upon acute insult (12).…”

Section: Discussionmentioning

confidence: 99%

“…LPS was dissolved in physiological saline and administered i.p. with a dose of 2.5mg/kg as used in previous studies (1, 10-12). The dose of LPS given to DR mice was calculated based on original body weight prior to weight loss.…”

Section: Methodsmentioning

confidence: 99%

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Short-Term Dietary Restriction Rescues Mice From Lethal Abdominal Sepsis and Endotoxemia and Reduces the Inflammatory/Coagulant Potential of Adipose Tissue

Starr

Steele

Cohen

et al. 2016

Critical Care Medicine

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Objective Visceral adipose tissue is a major site for expression of pro-inflammatory and pro-coagulant genes during acute systemic inflammation. In this study, we tested whether loss of fat mass by dietary restriction (DR) would remove the major source of these factors resulting in improved tolerance to sepsis and endotoxemia. Design Prospective, laboratory controlled experiments. Setting Aging and Critical Care Research Laboratory in a university hospital. Subjects Middle-aged (12 month-old) male C57BL/6 mice. Interventions Mice were subjected to 40% DR for three weeks followed by induction of abdominal sepsis or endotoxemia by intraperitoneal injection with cecal slurry or lipopolysaccharide (LPS), respectively. Measurements and main results Compared to freely-fed mice, DR mice exhibited dramatically improved survival (80% vs 0% after sepsis, p<0.001;86% vs 12%after endotoxemia, p=0.013) and significantly reduced visceral fat-derived mRNA expression of interleukin-6 (IL-6), thrombospondin-1, plasminogen activator inhibitor-1, and tissue factor which positively correlated with fat mass. Plasma levels of IL-6 were significantly reduced by DR and correlated with adipose IL-6 mRNAlevels and fat mass (p<0.001, R2=0.64 and 0.89). In vitro culture of visceral fat explants from naïve DR mice showed significantly reduced IL-6 secretion compared to that from freely-fed mice in response to LPS. Analysis of major adipose immune cell populations by flow cytometry demonstrated that macrophages were the only cell population reduced by DR and that CD11c+/CD206+ (M2-type) and CD11c-/CD206- (double negative) macrophages, in addition to T cells, are the major immune cell populations that produce IL-6 in middle-age during systemic inflammation. Conclusions Short-term DR drastically improved the survival outcome of middle-aged mice during both polymicrobial sepsis and sterile endotoxemia. Improved survival was accompanied by a significantly attenuated inflammatory response in adipose tissue, which is likely due to alterations of both fat mass quantity and qualitative changes including a reduction in macrophage populations.

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Age-Associated Increase in Cytokine Production During Systemic Inflammation—II: The Role of IL-1β in Age-Dependent IL-6 Upregulation in Adipose Tissue

Cited by 73 publications

References 49 publications

Cellular senescence in aging and age-related disease: from mechanisms to therapy

Cellular senescence in aging and age-related disease: from mechanisms to therapy

Habitual physical activity protects against lipopolysaccharide-induced inflammation in mouse adipose tissue

Short-Term Dietary Restriction Rescues Mice From Lethal Abdominal Sepsis and Endotoxemia and Reduces the Inflammatory/Coagulant Potential of Adipose Tissue

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