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Cellular senescence in normal and premature lung aging

Zelluläre Seneszenz bei normaler und verfrühter Lungenalterung

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Abstract

The incidence of chronic respiratory diseases (e.g., chronic obstructive pulmonary disease, COPD) and interstitial lung diseases (e.g., pneumonia and lung fibrosis) increases with age. In addition to immune senescence, the accumulation of senescent cells directly in lung tissue might play a critical role in the increased prevalence of these pulmonary diseases. In the last couple of years, detailed studies have identified the presence of senescent cells in the aging lung and in diseased lungs of patients with COPD and lung fibrosis. Cellular senescence has been shown for epithelial cells of bronchi and alveoli as well as mesenchymal and vascular cells. Known risk factors for pulmonary diseases (cigarette smoke, air pollutions, bacterial infections, etc.) were identified in experimental studies as being possible mediators in the development of cellular senescence. The present findings indicate the importance of cellular senescence in normal lung aging and in premature aging of the lung in patients with COPD, lung fibrosis, and probably other respiratory diseases.

Zusammenfassung

Chronische Atemwegserkrankungen, insbesondere die chronisch obstruktive Lungenerkrankung (COPD), sowie interstitielle Lungenerkrankungen wie die Pneumonie und die Lungenfibrose nehmen mit dem Alter deutlich zu. Dabei könnte neben der Immunseneszenz auch das vermehrte Auftreten von seneszenten Zellen direkt in der Lunge eine wichtige Rolle spielen. In den letzten Jahren wiesen detaillierte Studien seneszente Zellen in der alten Lunge und in der erkrankten Lunge von Patienten mit COPD oder Lungenfibrose nach. Neben den epithelialen Zellen von Bronchien und Alveolen waren von der Seneszenz auch Bindegewebszellen und Gefäßzellen betroffen. Mithilfe experimenteller Studien wurden bekannte Risikofaktoren von Atemwegserkrankungen (Zigarettenrauch, Luftverschmutzung, bakterielle Infektionen etc.) als mögliche Auslöser der zellulären Seneszenz identifiziert. Die Erkenntnisse weisen auf die Bedeutung der zellulären Seneszenz bei der normalen Lungenalterung hin, aber auch bei der verfrühten Alterung der Lunge bei Patienten mit COPD, Lungenfibrose oder möglicherweise anderen Atemwegserkrankungen.

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Abbreviations

53BP1:

p53-binding protein-1

ATM:

ataxia telangiectasia-mutated

ATR:

ATM- and Rad-3-related kinase

CDC:

cell division cycle

CDK:

cyclin-dependent kinase

Chk:

checkpoint kinase

COPD:

chronic obstructive pulmonary disease

CKI:

cyclin-dependent kinase inhibitor

DDR:

DNA damage response

DNA-PK:

DNA-dependent protein kinase

ds:

double stand

GADD45:

growth arrest and DNA damage 45

HR:

homologue recombination

hTERT:

telomerase catalytic subunit

IPF:

idiopathic pulmonary fibrosis

ICD-10:

international statistical classification of diseases and related health problems, version 10

IL:

interleukin

MAPK:

mitogen-activated protein kinase

MCP-1:

monocyte chemotactic protein-1

mTOR:

mammalian target of rapamycin

NAD:

nicotinamide adenine dinucleotide

NHEJ:

non-homologue end-joining

NF-κB:

nuclear factor κ-light-chain-enhancer of activated B-cells

P:

phosphorylated

p16Ink4a :

protein 16 (CKI 2A)

p19Arf :

protein 19 (CKI 2A)

p21Cip1/Waf1 :

protein 21 (cyclin-dependent kinase inhibitor protein 1A)

p53:

protein 53

pRb:

retinoblastoma susceptibility protein

SA:

senescence-associated

SAHF:

senescence-associated heterochromatin foci

SAM:

senescence accelerated mouse

SIRT:

sirtuin (silent mating type information regulation)

Src:

Swiss raid commando

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Conflict of interest. B. Bartling states that there are no conflicts of interests.

The accompanying manuscript does not include studies on humans or animals.

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  1. Klinik und Poliklinik für Herz- und Thoraxchirurgie, Universitätsklinikum Halle (Saale) AöR, Ernst-Grube-Str. 40, 06120, Halle (Saale), Germany

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Bartling, B. Cellular senescence in normal and premature lung aging. Z Gerontol Geriat 46, 613–622 (2013). https://doi.org/10.1007/s00391-013-0543-3

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