TY - JOUR
T1 - DAMPs, ageing, and cancer
T2 - The 'DAMP Hypothesis'
AU - Huang, Jin
AU - Xie, Yangchun
AU - Sun, Xiaofang
AU - Zeh, Herbert J.
AU - Kang, Rui
AU - Lotze, Michael T.
AU - Tang, Daolin
N1 - Funding Information:
We thank Christine Heiner (Department of Surgery/Department of Anesthesiology, University of Pittsburgh) for her critical reading of the manuscript. Work done in support of findings reviewed in this manuscript was aided by the Core Support of the UPCI ( P30CA047904 to Davidson). This work was also supported by the National Institutes of Health ( R01 CA160417 to DT; R01 CA181450 to HJZ/MTL), and a 2013 Pancreatic Cancer Action Network-AACR Career Development Award (Grant Number 13-20-25-TANG ).
Publisher Copyright:
© 2014 Elsevier B.V.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - Ageing is a complex and multifactorial process characterized by the accumulation of many forms of damage at the molecular, cellular, and tissue level with advancing age. Ageing increases the risk of the onset of chronic inflammation-associated diseases such as cancer, diabetes, stroke, and neurodegenerative disease. In particular, ageing and cancer share some common origins and hallmarks such as genomic instability, epigenetic alteration, aberrant telomeres, inflammation and immune injury, reprogrammed metabolism, and degradation system impairment (including within the ubiquitin-proteasome system and the autophagic machinery). Recent advances indicate that damage-associated molecular pattern molecules (DAMPs) such as high mobility group box 1, histones, S100, and heat shock proteins play location-dependent roles inside and outside the cell. These provide interaction platforms at molecular levels linked to common hallmarks of ageing and cancer. They can act as inducers, sensors, and mediators of stress through individual plasma membrane receptors, intracellular recognition receptors (e.g., advanced glycosylation end product-specific receptors, AIM2-like receptors, RIG-I-like receptors, and NOD1-like receptors, and toll-like receptors), or following endocytic uptake. Thus, the DAMP Hypothesis is novel and complements other theories that explain the features of ageing. DAMPs represent ideal biomarkers of ageing and provide an attractive target for interventions in ageing and age-associated diseases.
AB - Ageing is a complex and multifactorial process characterized by the accumulation of many forms of damage at the molecular, cellular, and tissue level with advancing age. Ageing increases the risk of the onset of chronic inflammation-associated diseases such as cancer, diabetes, stroke, and neurodegenerative disease. In particular, ageing and cancer share some common origins and hallmarks such as genomic instability, epigenetic alteration, aberrant telomeres, inflammation and immune injury, reprogrammed metabolism, and degradation system impairment (including within the ubiquitin-proteasome system and the autophagic machinery). Recent advances indicate that damage-associated molecular pattern molecules (DAMPs) such as high mobility group box 1, histones, S100, and heat shock proteins play location-dependent roles inside and outside the cell. These provide interaction platforms at molecular levels linked to common hallmarks of ageing and cancer. They can act as inducers, sensors, and mediators of stress through individual plasma membrane receptors, intracellular recognition receptors (e.g., advanced glycosylation end product-specific receptors, AIM2-like receptors, RIG-I-like receptors, and NOD1-like receptors, and toll-like receptors), or following endocytic uptake. Thus, the DAMP Hypothesis is novel and complements other theories that explain the features of ageing. DAMPs represent ideal biomarkers of ageing and provide an attractive target for interventions in ageing and age-associated diseases.
KW - Ageing
KW - Biomarker
KW - Cancer
KW - Damage-associated molecular pattern (DAMP) molecules
KW - Longevity
KW - Receptor
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U2 - 10.1016/j.arr.2014.10.004
DO - 10.1016/j.arr.2014.10.004
M3 - Review article
C2 - 25446804
AN - SCOPUS:84946845377
SN - 1568-1637
VL - 24
SP - 3
EP - 16
JO - Ageing Research Reviews
JF - Ageing Research Reviews
ER -