title: DAMPs, ageing, and cancer: The 'DAMP Hypothesis'.
abstract: 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.
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China; Departments of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Yangchun
authors.initials: Y
authors.lastname: Xie
authors.affiliation: The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510510, Guangdong, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Sun
authors.affiliation: Departments of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Zeh
authors.affiliation: Departments of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Kang
authors.affiliation: Departments of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA; Immunology and Bioengineering, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lotze
authors.affiliation: Departments of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA. Electronic address: tangd2@upmc.edu.
authors.forename: Daolin
authors.initials: D
authors.lastname: Tang
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051192:Receptors, Pattern Recognition / Q000378:metabolism*
chemical_list: D051192:Receptors, Pattern Recognition
keywords: Ageing; Biomarker; Cancer; Damage-associated molecular pattern (DAMP) molecules; Longevity; Receptor