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. 2019 May 11;8(2):40. doi: 10.3390/biology8020040

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© 2019 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Integrated Systems Hypothesis of Aging (see text for details). DAMPs: danger-associated molecular patterns; ER: endoplasmic reticulum; CDR: cell danger response; DDR: DNA danger response; Inflammaging: chronic, low-grade inflammation with aging; SASP: senescence-associated secretory phenotype; Gerokines: cytokines, chemokines, growth factors, and proteases increased with aging; Vicious cycle: self-reinforcing feedback loop with detrimental outcome(s); NLRP3: inflammasome; P16: tumor suppressor protein P16^INK4A/CDKN2A; P21: tumor suppressor protein P21^Cip1/CDKN1A; IL: interleukin; TNF: tumor necrosis factor; CXCL-1: chemokine (C-X-C motif) ligand 1 (also KC and GROα); GM-CSF: granulocyte-macrophage colony-stimulating factor.