Table 2.

Senescence-related processes reported in CF

Senescence-related process	Comparison with CF condition	Ref
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]