Table 2 Senescence-related processes reported in CF

Increased PMN recruitment into the bronchial lumen with ageing

Increased PMN recruitment within the bronchial lumen associated with increased release of chemokines

[23, 30, 36]

SASP release

Increased levels of IL-6, IL-8, IL-1β GROα and TGF-β

[15, 32, 65, 77, 91]

Dysregulated apoptosis: SASP and defective autophagy induce apoptosis, whereas ageing reduces apoptosis, promotes carcinogenesis and reduces immunosurveillance.

Increased apoptosis mediated by cytokines and ceramide accumulation in lung epithelia and a p21-dependent decrease in the apoptotic rate of PMNs.

[25, 106, 111, 112]

Increased NE release with ageing due to accumulation of PMNs

Early increase in NE accumulation into the bronchial lumen due to excessive accumulation of PMNs

[23, 30, 36]

Mitochondrial stress

Increased ROS levels and ATP release due to mitochondrial impairment

[48, 57, 60, 62]

Inflammasome activation

NRLP3-mediated inflammasome activation and increased IL-1β release

[36, 48, 53, 65]

mTOR-dependent increase in SASP with subsequent upregulation of the NF-κB pathway

Upregulated mTOR activity is linked to decreased CFTR stability and expression.

[8, 10, 12, 14, 52]

Increased p21 activation mediated by upregulation of the p53 pathway

Upregulation of the p21 pathway in PMNs and bronchial epithelial cells, mediated by mitochondrial stress signalling.

[23, 24, 26, 140]

Increased p38 MAPK signalling transduction

p38 pathway upregulation leading to NF-κB activation in bronchial epithelia

[32, 75, 86]

NF-κB and C/EBPβ increased activation

Increased NF-κB and C/EBPβ nuclear translocation associated with increased cytokine expression in bronchial epithelia

[32, 73, 75, 86]

Cav-1 involvement in SASP

Loss of CFTR expression leads to Cav-1 upregulation and a subsequent increase in cytokine release and NF-κB activation.

[89, 90]