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.
Highlights
Immune insufficiency and the rate of infections are known to increase considerably with age [1]
At postnatal day 3, the recuperated pups were lighter than controls (6.3 ± 0.2 compared with 7.4 ± 0.2 g) (p
A sub-optimal maternal diet during pregnancy followed by a mismatched postnatal milieu increases the risk of developing age-associated diseases, the extent that
Summary
Immune insufficiency and the rate of infections are known to increase considerably with age [1]. ‘The Thrifty Phenotype Hypothesis’ was postulated over 25 years ago by Hales and Barker [4] to explain the phenomenon of increased risk of developing age-associated diseases such as cardiovascular disease (CVD) and type-2 diabetes (T2D) when individuals were exposed to conditions of suboptimal maternal nutrition during fetal life. Under these conditions, the fetus is “developmentally programmed” resulting in structural changes to organ development and adaptions to its metabolism to ensure immediate postnatal survival of the organism. Despite decline in immune function being known to play an important role in the development of many age-associated diseases, it has been poorly studied in the context of developmental programming
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