METHODS: Total
RNA from the human lung tissues of non-smokers, smokers, and patients with
COPD and IPF were processed and analyzed using a Nanostring platform based on their ages (younger: <55 years and older: >55 years).
RESULTS: Several genes were differentially expressed in younger and older smokers, and patients with
COPD and IPF compared to non-smokers which were part of the mitochondrial biogenesis/function (HSPD1, FEN1, COX18, COX10, UCP2 & 3), cellular senescence (
PCNA, PTEN, KLOTHO, CDKN1C, TNKS2, NFATC1 & 2, GADD45A), and telomere replication/maintenance (PARP1, SIRT6, NBN, TERT, RAD17, SLX4, HAT1) target genes. Interestingly, NOX4 and TNKS2 were increased in the young IPF as compared to the young
COPD patients. Genes in the mitochondrial dynamics and quality control mechanisms like FIS1 and RHOT2 were decreased in young IPF compared to their age matched
COPD subjects. ERCC1 and GADD45B were higher in young
COPD as compared to IPF. Aging plays an important role in various
infectious diseases including the
SARS-CoV-2 infection. Lung immunoblot analysis of smokers,
COPD and IPF subjects revealed increased abundance of
proteases and receptor/spike
protein like TMPRSS2,
furin, and DPP4 in association with a slight increase in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor ACE2 levels.
CONCLUSIONS: Overall, these findings suggest that altered transcription of target genes that regulate mitochondrial function, cellular senescence, and telomere attrition in the pathobiology of lung aging in
COPD and IPF is associated with alterations in SARS-CoV-2 ACE2-TMPRSS2-Furin-DPP4 axis as pharmacological targets for
COVID-19.