title: Autophagy Controls Acquisition of Aging Features in Macrophages.
abstract: Macrophages provide a bridge linking innate and adaptive immunity. An increased frequency of macrophages and other myeloid cells paired with excessive cytokine production is commonly seen in the aging immune system, known as 'inflamm-aging'. It is presently unclear how healthy macrophages are maintained throughout life and what connects inflammation with myeloid dysfunction during aging. Autophagy, an intracellular degradation mechanism, has known links with aging and lifespan extension. Here, we show for the first time that autophagy regulates the acquisition of major aging features in macrophages. In the absence of the essential autophagy gene Atg7, macrophage populations are increased and key functions such as phagocytosis and nitrite burst are reduced, while the inflammatory cytokine response is significantly increased - a phenotype also observed in aged macrophages. Furthermore, reduced autophagy decreases surface antigen expression and skews macrophage metabolism toward glycolysis. We show that macrophages from aged mice exhibit significantly reduced autophagic flux compared to young mice. These data demonstrate that autophagy plays a critical role in the maintenance of macrophage homeostasis and function, regulating inflammation and metabolism and thereby preventing immunosenescence. Thus, autophagy modulation may prevent excess inflammation and preserve macrophage function during aging, improving immune responses and reducing the morbidity and mortality associated with inflamm-aging.
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Stranks
authors.forename: Anne Louise
authors.initials: AL
authors.lastname: Hansen
authors.forename: Isabel
authors.initials: I
authors.lastname: Panse
authors.forename: Monika
authors.initials: M
authors.lastname: Mortensen
authors.forename: David J P
authors.initials: DJ
authors.lastname: Ferguson
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Puleston
authors.forename: Kevin
authors.initials: K
authors.lastname: Shenderov
authors.forename: Alexander Scarth
authors.initials: AS
authors.lastname: Watson
authors.forename: Marc
authors.initials: M
authors.lastname: Veldhoen
authors.forename: Kanchan
authors.initials: K
authors.lastname: Phadwal
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerundolo
authors.forename: Anna Katharina
authors.initials: AK
authors.lastname: Simon
mesh_terms: D000375:Aging / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000276:immunology*; D000071193:Autophagy-Related Protein 7; D006019:Glycolysis / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: C502661:Atg7 protein, mouse; D008869:Microtubule-Associated Proteins; D000071193:Autophagy-Related Protein 7