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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：

AIM: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.

journal_name

Geriatr Gerontol Int

journal_title

Geriatrics & gerontology international

authors

Ishii T,Gemma A,Kida K

doi

10.1111/ggi.12354

subject

Has Abstract

pub_date

2015-07-01 00:00:00

pages

827-33

issue

eissn

1444-1586

issn

1447-0594

journal_volume

pub_type

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Senescence is involved in the pathogenesis of chronic obstructive pulmonary disease through effects on telomeres and the anti-aging molecule fibroblast growth factor 23.