Advances in cellular senescence in idiopathic pulmonary fibrosis (Review)

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible and fatal interstitial lung disease of unknown cause, with a median survival of 2-3 years. Its pathogenesis is unclear and there is currently no effective treatment for IPF. Approximately two-thirds of patients with IPF are >60 years old, with a mean age of 66 years, suggesting a link between aging and IPF. However, the mechanism by which aging promotes development of PF remains unclear. Senescence of alveolar epithelial cells and lung fibroblasts (LFs) and their senescence-associated secretion phenotype (SASP) may be involved in the occurrence and development of IPF. The present review focus on senescence of LFs and epithelial and stem cells, as well as SASP, the activation of profibrotic signaling pathways and potential treatments for pathogenesis of IPF. Contents1. Introduction 2. Senescence of AECs and IPF 3. Senescence of fibroblasts and IPF 4. Stem cell senescence and IPF 5. SASP 6. Interaction between senescent ATII, LF and other cell types in IPF 7. Senotherapeutics 8. Conclusion

Cellular Senescence: A Troy Horse in Pulmonary Fibrosis

“…In contrast to young non-pathological fibroblasts, senescent fibroblasts in culture do not grow in an ordered parallel geometry, and their growth direction is random. In addition, these senescent lung fibroblasts also increased the levels of senescence-associated β-galactosidase, p21, p53, p16, and SASP [125][126][127].…”

Pulmonary Fibrosis and Diabetes Mellitus: Two coins with the same face

“…But fibroblasts per se also become senescent, and express high levels of SA-β-gal and cell cycle inhibitors like P16, P21 and P53 [ 29 ]. Mitochondrial dysfunction, telomere shortening, epigenetic modifications, DNA damage, protein homeostatic imbalance and decreased autophagy are among factors involved in IPF [ 30 ]. Inhibition of autophagy has been related to accelerated senescence in epithelial cells, enhanced EMT and fibrosis [ 31 ].…”

Sirtuins and Cellular Senescence in Patients with Idiopathic Pulmonary Fibrosis and Systemic Autoimmune Disorders

“…Notably, the activation or overexpression of SIRT1 by resveratrol treatment attenuates the TGF-β1-induced myofibroblast activation by regulating the expression of p300 [ 35 ]. In addition, SIRT1 suppresses the expression of senescence-associated secretory phenotype (SASP) factors through histone deacetylation in their promoter regions, resulting in an antifibrotic effect [ 36 ]. Lian et al found decreased levels of the zinc transporter SLC39A8 (ZIP8) in IPF AEC2s, resulting in impaired renewal capacity dependent on the sirtuin SIRT1.…”