title: Proteasome function is not impaired in healthy aging of the lung.
abstract: Aging is the progressive loss of cellular function which inevitably leads to death. Failure of proteostasis including the decrease in proteasome function is one hallmark of aging. In the lung, proteasome activity was shown to be impaired in age-related diseases such as chronic obstructive pulmonary disease. However, little is known on proteasome function during healthy aging. Here, we comprehensively analyzed healthy lung aging and proteasome function in wildtype, proteasome reporter and immunoproteasome knockout mice. Wildtype mice spontaneously developed senile lung emphysema while expression and activity of proteasome complexes and turnover of ubiquitinated substrates was not grossly altered in lungs of aged mice. Immunoproteasome subunits were specifically upregulated in the aged lung and the caspase-like proteasome activity concomitantly decreased. Aged knockout mice for the LMP2 or LMP7 immunoproteasome subunits showed no alteration in proteasome activities but exhibited typical lung aging phenotypes suggesting that immunoproteasome function is dispensable for physiological lung aging in mice. Our results indicate that healthy aging of the lung does not involve impairment of proteasome function. Apparently, the reserve capacity of the proteostasis systems in the lung is sufficient to avoid severe proteostasis imbalance during healthy aging.
authors.affiliation: Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, Helmholtz Zentrum München, Munich, Member of the German Center for Lung Research (DZL), Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Caniard
authors.affiliation: Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, Helmholtz Zentrum München, Munich, Member of the German Center for Lung Research (DZL), Germany.
authors.forename: Korbinian
authors.initials: K
authors.lastname: Ballweg
authors.affiliation: Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, Helmholtz Zentrum München, Munich, Member of the German Center for Lung Research (DZL), Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Lukas
authors.affiliation: Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, Helmholtz Zentrum München, Munich, Member of the German Center for Lung Research (DZL), Germany.
authors.forename: Ali Ö
authors.initials: AÖ
authors.lastname: Yildirim
authors.affiliation: Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, Helmholtz Zentrum München, Munich, Member of the German Center for Lung Research (DZL), Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Eickelberg
authors.affiliation: Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, Helmholtz Zentrum München, Munich, Member of the German Center for Lung Research (DZL), Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Meiners
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D003546:Cysteine Endopeptidases / Q000172:deficiency; D005260:Female; D008168:Lung / Q000201:enzymology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046988:Proteasome Endopeptidase Complex / Q000172:deficiency / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D025801:Ubiquitin; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex
keywords: LMP2; emphysema; immunoproteasome; proteasome; proteostasis