A suboptimal maternal diet combined with accelerated postnatal growth results in an altered aging profile in the thymus of male rats.
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Authors
Tarry-Adkins, Jane L
Aiken, Catherine E
Ashmore, Thomas J
Fernandez-Twinn, Denise S
Chen, Jian-Hua
Ozanne, Susan E
Publication Date
2019-01Journal Title
FASEB J
ISSN
0892-6638
Publisher
Wiley
Volume
33
Issue
1
Pages
239-253
Language
eng
Type
Article
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Tarry-Adkins, J. L., Aiken, C. E., Ashmore, T. J., Fernandez-Twinn, D. S., Chen, J., & Ozanne, S. E. (2019). A suboptimal maternal diet combined with accelerated postnatal growth results in an altered aging profile in the thymus of male rats.. FASEB J, 33 (1), 239-253. https://doi.org/10.1096/fj.201701350RR
Abstract
Reduced fetal nutrition and rapid postnatal growth accelerates the aging phenotype in many organ 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 cross-fostering 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 thymocyte markers ( 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-length maintenance molecules [telomerase RNA component ( Terc; P < 0.01), P23 ( P = 0.02), and Ku70 and Ku80 ( 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 γ-H2ax ( P < 0.001], suggesting failure of earlier compensatory responses. Our results suggest that low birth weight with rapid postnatal growth results in premature thymic maturation, resulting in accelerated thymic aging. This could lead to increased age-associated vulnerability to infection.-Tarry-Adkins, J. L., Aiken, C. E., Ashmore, T. J., Fernandez-Twinn, D. S., Chen, J.-H., Ozanne, S. E. A suboptimal maternal diet combined with accelerated postnatal growth results in an altered aging profile in the thymus of male rats.
Keywords
Thymus Gland, Animals, Rats, Rats, Wistar, Malnutrition, DNA Damage, Diet, Oxidative Stress, Aging, Female, Male, Maternal Nutritional Physiological Phenomena, Telomere Shortening, Biomarkers, Cellular Senescence
Sponsorship
British Heart Foundation (None)
Medical Research Council (MC_UU_12012/4)
British Heart Foundation (None)
MRC (MC_UU_00014/4)
British Heart Foundation (RG/17/12/33167)
Identifiers
External DOI: https://doi.org/10.1096/fj.201701350RR
This record's URL: https://www.repository.cam.ac.uk/handle/1810/279570
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