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Aging and disease    2019, Vol. 10 Issue (2) : 367-382     DOI: 10.14336/AD.2018.0324
Review |
Redefining Chronic Inflammation in Aging and Age-Related Diseases: Proposal of the Senoinflammation Concept
Hae Young Chung1,*, Dae Hyun Kim1, Eun Kyeong Lee1,2, Ki Wung Chung1, Sangwoon Chung3, Bonggi Lee4, Arnold Y. Seo5, Jae Heun Chung6, Young Suk Jung1, Eunok Im1, Jaewon Lee1, Nam Deuk Kim1, Yeon Ja Choi7, Dong Soon Im1,*, Byung Pal Yu8,*
1Molecular Inflammation Research Center for Aging Intervention (MRCA), Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 609-735, Korea.
2Pathological and Analytical Center, Korea Institute of Toxicology, Daejeon 34114, Korea.
3Department of Internal Medicine, Pulmonary, Allergy, Critical Care & Sleep Medicine, The Ohio State University, Columbus, OH 43210, USA.
4Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Daegu 41062, Republic of Korea.
5Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
6Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, Korea.
7Department of Biopharmaceutical Engineering, Division of Chemistry and Biotechnology, Dongguk University, Gyeongju 38066, Korea.
8Department of Physiology, The University of Texas Health Science Center at San Antonio, TX 78229, USA.
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Abstract  

Age-associated chronic inflammation is characterized by unresolved and uncontrolled inflammation with multivariable low-grade, chronic and systemic responses that exacerbate the aging process and age-related chronic diseases. Currently, there are two major hypotheses related to the involvement of chronic inflammation in the aging process: molecular inflammation of aging and inflammaging. However, neither of these hypotheses satisfactorily addresses age-related chronic inflammation, considering the recent advances that have been made in inflammation research. A more comprehensive view of age-related inflammation, that has a scope beyond the conventional view, is therefore required. In this review, we discuss newly emerging data on multi-phase inflammatory networks and proinflammatory pathways as they relate to aging. We describe the age-related upregulation of nuclear factor (NF)-κB signaling, cytokines/chemokines, endoplasmic reticulum (ER) stress, inflammasome, and lipid accumulation. The later sections of this review present our expanded view of age-related senescent inflammation, a process we term “senoinflammation”, that we propose here as a novel concept. As described in the discussion, senoinflammation provides a schema highlighting the important and ever-increasing roles of proinflammatory senescence-associated secretome, inflammasome, ER stress, TLRs, and microRNAs, which support the senoinflammation concept. It is hoped that this new concept of senoinflammation opens wider and deeper avenues for basic inflammation research and provides new insights into the anti-inflammatory therapeutic strategies targeting the multiple proinflammatory pathways and mediators and mediators that underlie the pathophysiological aging process.

Keywords chronic inflammation      senoinflammation      aging      senescence-associated secretome      inflammasome      age-related diseases     
Corresponding Authors: Chung Hae Young,Im Dong Soon,Yu Byung Pal   
About author:

These authors contributed equally to this study.

Issue Date: 22 February 2017
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Hae Young Chung
Dae Hyun Kim
Eun Kyeong Lee
Ki Wung Chung
Sangwoon Chung
Bonggi Lee
Arnold Y. Seo
Jae Heun Chung
Young Suk Jung
Eunok Im
Jaewon Lee
Nam Deuk Kim
Yeon Ja Choi
Dong Soon Im
Byung Pal Yu
Cite this article:   
Hae Young Chung,Dae Hyun Kim,Eun Kyeong Lee, et al. Redefining Chronic Inflammation in Aging and Age-Related Diseases: Proposal of the Senoinflammation Concept[J]. Aging and disease, 2019, 10(2): 367-382.
URL:  
http://www.aginganddisease.org/EN/10.14336/AD.2018.0324     OR     http://www.aginganddisease.org/EN/Y2019/V10/I2/367
Figure 1.  Schematic representation of the senoinflammation concept. MMP, matrix metalloproteinase; Infla-genes, proinflammatory genes; ER, endoplasmic reticulum; TLRs, Toll-like receptors; HMGB1, high-mobility group box 1; RAGE, receptor for advanced glycation end product.
SASP FactorsSenescent cellsAged tissuesHuman tissues
Cytokines, chemokines, and regulators
IL-1α↑↑↑-
IL-1β↑↑↑↑
IL-6↑↑↑↑↑↑
IL-7↑↑↑↑↑
IL-13↑↑-
IL1R1
IL11↑↑↑
IL15-
IL6R↑↑
IL27Rα-
IL2RA↑↑↑
IL-8↑↑↑-
GRO-α (CXCL1)↑↑↑-
GRO-β (CXCL2)↑↑↑-
GRO-γ (CXCL3)↑↑↑-
MCP-1 (CCL2)↑↑↑↑↑↑
MCP-2↑↑↑-
MIP-1α (CCL3)↑↑↑-
MIP-3α↑↑↑↑↑
TNF-α-
TNF-β-↑↑
sTNFRI(TNFRSF1B)↑↑
OPG(TNFRSF11B)↑*
Other proinflammatory factors
MMP1↑↑↑-
MMP3↑↑↑↑↑
MMP10↑↑↑-
MMP12↑↑↑↑↑
MMP13↑↑-
MMP14↑↑-
TIMP1↑↑↑
iNOS-↑↑↑
IGFBP2-
IGFBP3↑*
IGFBP6
HGF
EGFR
FAS
Reference144-14624, 125TCGA data base
Table 1  Proinflammatory SA secretome in senescent cells, aged tissues, and human tissues.
Age-related inflammation/molecular inflammationInflammagingSenoinflammation
OxidationSirt1, PPAR, FOXOs, SOD, CAT, PTK/PTPSirt1, NotchFOXOs, SOD, CAT, LCK, SRC, PTK/PTP
InflammationCOX-2, iNOS, TNFα, IL-1,6, AMsTNFα, IL-6COX-2, iNOS, TNFα, IL-1,6
Cytokine/ChemokinesIL-7, IL-2RA, CXCL1,2,3, MCP-1, CCL3TGFβ, IL-8, TNFαcytokines, chemokines, MMPs, GFs, IGFBPs
Apoptosisp53, p21, Bax
AutophagymTORmTORmTOR
Dysregulated metabolismleptin, adiponectin, anabolism, catabolism
ER stressIRE, PERK, ATF4,6
Insulin resistanceIRS-Ser-p, Akt
InflammasomeNLRP3
Reference6-9, 12-1510, 11, 546-9, 12-15, 23-25, 42, 125
Table 2  Comparison of major key features defining age-related chronic inflammation.
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