title: Age-related decline of mast cell regeneration in senescence-accelerated mice (SAMP1) after chemical myeloablation due to senescent stromal cell impairment.
abstract: An age-related decline in immune functions is referred to as immunosenescence. Mast cells play an important role in the immune system. However, it has not yet been determined if aging may affect mast-cell development. In the present study, we examined the age-related change in mast-cell development after myeloablation with 5-fluorouracil (5-FU) in senescence accelerated mice (SAMP1), which exhibit senescence-mimicking stromal cell impairment after 30 weeks of age. We found that aged mice with stromal cell impairment (30-36 weeks old) showed a lower recovery of the number of femoral mast-cell progenitors (colony-forming unit [CFU]-mast) (64% of steady state), whereas young mice (8-12 weeks old) showed a higher recovery (122% of steady state). Stromal cells influence mast-cell development by producing positive regulators such as stem cell factor (SCF) and negative regulators such as transforming growth factor-beta (TGF-β). The ratio of the gene expression of SCF to that of TGF-β (SCF/TGF-β ratio) indicates the balance of positive and negative regulation of mast-cell development. SCF/TGF-β ratio increased in both the young and aged mice after 5-FU treatment. However, the SCF/TGF-β ratio rapidly decreased in aged mice, whereas it remained high in young mice. The number of femoral CFU-mast in the S-phase after 5-FU treatment reflects the activation of positive-dominant regulation for mast-cell development by stromal cells. Aged mice showed lower recovery of the number of femoral CFU-mast in the S-phase (47% of steady state), whereas young mice showed a higher recovery (205% of steady state). These results suggest that mast-cell development declines with aging due to stromal-cell functional impairment, which contributes to immunosenescence.
authors.affiliation: Department of Functional Morphology, Nihon University School of Medicine, Ohyaguchi-kami-machi, Itabashiku, Tokyo. tsuboi@med.nihon-u.ac.jp
authors.forename: Isao
authors.initials: I
authors.lastname: Tsuboi
authors.forename: Tomonori
authors.initials: T
authors.lastname: Harada
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hirabayashi
authors.forename: Jun
authors.initials: J
authors.lastname: Kanno
authors.forename: Tohru
authors.initials: T
authors.lastname: Inoue
authors.forename: Shin
authors.initials: S
authors.lastname: Aizawa
mesh_terms: D000375:Aging / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D005269:Femur / Q000187:drug effects / Q000378:metabolism; D005472:Fluorouracil / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D016196:S Phase / Q000187:drug effects / Q000235:genetics; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D019089:Stem Cell Factor; D016212:Transforming Growth Factor beta; D005472:Fluorouracil