TY - JOUR
T1 - Biomarkers of cellular senescence in idiopathic pulmonary fibrosis
AU - Aversa, Zaira
AU - Atkinson, Elizabeth J.
AU - Carmona, Eva M.
AU - White, Thomas A.
AU - Heeren, Amanda A.
AU - Jachim, Sarah K.
AU - Zhang, Xu
AU - Cummings, Steven R.
AU - Chiarella, Sergio E.
AU - Limper, Andrew H.
AU - LeBrasseur, Nathan K.
N1 - Funding Information:
Supported by a Team Science Award from the Mayo Clinic CTSA grant number UL1TR000135 from the National Center for Advancing Translational Science (NCATS), a component of the National Institutes of Health (NIH) and a generous gift from the John E. and Virginia H. Kunkel Family (N.K.L); the National Institutes of Health, National Institute on Aging grants R56 AG 60907 and R01 AG55529 (N.K.L.); the Glenn Foundation for Medical Research (N.K.L). The Lung Tissue Research Consortium effort at our institution was supported by NHLBI Contract No. 268201600004I-0-26800002-1 to A.H.L.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - Background: Cellular senescence is a cell fate in response to diverse forms of age-related damage and stress that has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The associations between circulating levels of candidate senescence biomarkers and disease outcomes have not been specifically studied in IPF. In this study we assessed the circulating levels of candidate senescence biomarkers in individuals affected by IPF and controls and evaluated their ability to predict disease outcomes. Methods: We measured the plasma concentrations of 32 proteins associated with senescence in Lung Tissue Research Consortium participants and studied their relationship with the diagnosis of IPF, parameters of pulmonary and physical function, health-related quality of life, mortality, and lung tissue expression of P16, a prototypical marker of cellular senescence. A machine learning approach was used to evaluate the ability of combinatorial biomarker signatures to predict disease outcomes. Results: The circulating levels of several senescence biomarkers were significantly elevated in persons affected by IPF compared to controls. A subset of biomarkers accurately classified participants as having or not having the disease and was significantly correlated with measures of pulmonary function, health-related quality of life and, to an extent, physical function. An exploratory analysis revealed senescence biomarkers were also associated with mortality in IPF participants. Finally, the plasma concentrations of several biomarkers were associated with their expression levels in lung tissue as well as the expression of P16. Conclusions: Our results suggest that circulating levels of candidate senescence biomarkers are informative of disease status, pulmonary and physical function, and health-related quality of life. Additional studies are needed to validate the combinatorial biomarkers signatures that emerged using a machine learning approach.
AB - Background: Cellular senescence is a cell fate in response to diverse forms of age-related damage and stress that has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The associations between circulating levels of candidate senescence biomarkers and disease outcomes have not been specifically studied in IPF. In this study we assessed the circulating levels of candidate senescence biomarkers in individuals affected by IPF and controls and evaluated their ability to predict disease outcomes. Methods: We measured the plasma concentrations of 32 proteins associated with senescence in Lung Tissue Research Consortium participants and studied their relationship with the diagnosis of IPF, parameters of pulmonary and physical function, health-related quality of life, mortality, and lung tissue expression of P16, a prototypical marker of cellular senescence. A machine learning approach was used to evaluate the ability of combinatorial biomarker signatures to predict disease outcomes. Results: The circulating levels of several senescence biomarkers were significantly elevated in persons affected by IPF compared to controls. A subset of biomarkers accurately classified participants as having or not having the disease and was significantly correlated with measures of pulmonary function, health-related quality of life and, to an extent, physical function. An exploratory analysis revealed senescence biomarkers were also associated with mortality in IPF participants. Finally, the plasma concentrations of several biomarkers were associated with their expression levels in lung tissue as well as the expression of P16. Conclusions: Our results suggest that circulating levels of candidate senescence biomarkers are informative of disease status, pulmonary and physical function, and health-related quality of life. Additional studies are needed to validate the combinatorial biomarkers signatures that emerged using a machine learning approach.
KW - Aging
KW - Biomarkers
KW - Cellular senescence
KW - Idiopathic pulmonary fibrosis (IPF)
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U2 - 10.1186/s12931-023-02403-8
DO - 10.1186/s12931-023-02403-8
M3 - Article
C2 - 37029417
AN - SCOPUS:85152042203
SN - 1465-9921
VL - 24
JO - Respiratory Research
JF - Respiratory Research
IS - 1
M1 - 101
ER -