title: Senescence is involved in the pathogenesis of chronic obstructive pulmonary disease through effects on telomeres and the anti-aging molecule fibroblast growth factor 23.
abstract: OBJECTIVE
  Fibroblast growth factor 23 knockout mice develop premature aging and emphysema, indicating that dysregulation of the normal aging process is involved in the pathobiology of chronic obstructive pulmonary disease. Thus, we explored the association among a coding single-nucleotide polymorphism of fibroblast growth factor 23, its protein concentration in serum and telomere length in patients with chronic obstructive pulmonary disease.
  
  
  METHODS
  The study involved 361 smokers; among whom, 244 were patients with chronic obstructive pulmonary disease. We genotyped a coding single-nucleotide polymorphism of fibroblast growth factor 23, rs7955866, and measured the telomere length of the peripheral blood cells. We also determined emphysema severity and airflow obstruction using computed tomography and pulmonary function tests, respectively. Furthermore, we analyzed the association between the disease phenotypes and fibroblast growth factor 23 genotypes or telomere length of peripheral blood leukocytes, as well as the association between the serum level of the studied protein and its genotypes.
  
  
  RESULTS
  The mice with A alleles on rs7955866 showed severe upper lung emphysema (P = 0.008). The serum concentration of the tested protein was lower in the mice with A allele than in the G homozygotes (P = 0.004). Telomere shortening was associated with airflow obstruction (P = 0.009), but not with upper lung emphysema.
  
  
  CONCLUSIONS
  A variation of fibroblast growth factor 23 with a reduced serum concentration appeared to promote emphysema formation. Telomere shortening in peripheral blood leukocytes was not associated with emphysema, but with airflow obstruction in chronic obstructive pulmonary disease through an independent mechanism.
authors.affiliation: Respiratory Care Clinic, Nippon Medical School, Tokyo, Japan.|Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Ishii
authors.affiliation: Respiratory Care Clinic, Nippon Medical School, Tokyo, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Gemma
authors.affiliation: Respiratory Care Clinic, Nippon Medical School, Tokyo, Japan.|Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Kozui
authors.initials: K
authors.lastname: Kida
mesh_terms: D000368:Aged; D000375:Aging / Q000097:blood / Q000235:genetics*; D000818:Animals; D004247:DNA / Q000235:genetics*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D061330:Multidetector Computed Tomography; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics*; D016615:Telomere
chemical_list: D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D004247:DNA
keywords: aging; emphysema; fibroblast growth factor 23; genetic variation; telomere