A suboptimal maternal diet combined with accelerated postnatal growth results in an altered aging profile in the thymus of male rats

Jane L. Tarry-Adkins, Catherine Aiken, Thomas J. Ashmore, Denise S. Fernandez-Twinn, Jian Hua Chen, Susan E. Ozanne

Research output: Contribution to journalArticle

Abstract

Reduced fetal nutrition and rapid postnatal growth accelerates the aging phenotype inmanyorgan systems; however, effects on the immune system are unclear.We addressed this by studying the thymus from a rat model of developmental programming. The recuperated group was generated by in utero protein restriction, followed by crossfostering to control-fed mothers, and were then compared with controls. Fat infiltration and adipocyte size increased with age (P < 0.001) and in recuperated thymi (P < 0.05). Cortex/medulla ratio decreased with age (P < 0.001) and decreased (P < 0.05) in 12-mo recuperated thymi. Age-associated decreases in thymic-epithelial cell (P < 0.01) and thymocytemarkers (P < 0.01)were observed in both groups and was decreased (P < 0.05) in recuperated thymi. These data demonstrate effects of developmental programming upon thymic involution. The recuperated group had longer thymic telomeres than controls (P < 0.001) at 22 d and at 3 mo, which was associated with increased expression of telomere-lengthmaintenancemolecules [telomeraseRNAcomponent(Terc;P<0.01),P23 (P=0.02), andKu70andKu80 (P < 0.01)]. By 12 mo, recuperated offspring had shorter thymic telomeres than controls had (P < 0.001) and reduced DNA damage-response markers [(DNA-PKcs, Mre11 (P < 0.01), Xrcc4 (P = 0.02), and g-H2ax (P < 0.001], suggesting failure of earlier compensatory responses.Our results suggest that lowbirthweightwith rapidpostnatalgrowth results in premature thymic maturation, resulting in accelerated thymic aging. This could lead to increased age-associated vulnerability to infection.

Original languageEnglish (US)
Pages (from-to)239-253
Number of pages15
JournalFASEB Journal
Volume33
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

Thymus
Nutrition
Thymus Gland
Rats
Telomere
Aging of materials
Mothers
Diet
Growth
Immune system
DNA
Genetic Markers
Infiltration
Adipocytes
DNA Damage
Immune System
Epithelial Cells
Fats
Phenotype
Infection

Keywords

  • Developmental programming
  • Immunosenescence
  • Involution

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

A suboptimal maternal diet combined with accelerated postnatal growth results in an altered aging profile in the thymus of male rats. / Tarry-Adkins, Jane L.; Aiken, Catherine; Ashmore, Thomas J.; Fernandez-Twinn, Denise S.; Chen, Jian Hua; Ozanne, Susan E.

In: FASEB Journal, Vol. 33, No. 1, 01.01.2019, p. 239-253.

Research output: Contribution to journalArticle

Tarry-Adkins, Jane L. ; Aiken, Catherine ; Ashmore, Thomas J. ; Fernandez-Twinn, Denise S. ; Chen, Jian Hua ; Ozanne, Susan E. / A suboptimal maternal diet combined with accelerated postnatal growth results in an altered aging profile in the thymus of male rats. In: FASEB Journal. 2019 ; Vol. 33, No. 1. pp. 239-253.
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