DAMPs, ageing, and cancer: The 'DAMP Hypothesis'

Jin Huang, Yangchun Xie, Xiaofang Sun, Herbert J. Zeh, Rui Kang, Michael T. Lotze, Daolin Tang

Research output: Contribution to journalReview article

43 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3-16
Number of pages14
JournalAgeing Research Reviews
Volume24
DOIs
StatePublished - Nov 1 2015
Externally publishedYes

Keywords

  • Ageing
  • Biomarker
  • Cancer
  • Damage-associated molecular pattern (DAMP) molecules
  • Longevity
  • Receptor

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Aging
  • Molecular Biology
  • Neurology

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