Are rates of ageing determined <i>in utero</i>?

Sayer, Avan Aihie; Cooper, Cyrus; Evans, Jennifer R; Rauf, Abdul; Wormald, Richard; Osmond, Clive; Barker, D. J. P.

doi:10.1093/ageing/27.5.579

Cited by 146 publications

(102 citation statements)

References 13 publications

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“…Specific implications of our findings include the direct relationship between DNA hypomethylation and aging, particularly within the context of the "fetal origins of adult disease hypothesis" (50,53,62). Moreover, as summarized by Maier and Olek (33a), considerable indirect evidence exists that aberrant DNA methylation plays a role in the development of insulin resistance, not the least of which is finding of increased SAH levels in diabetes.…”

Section: Discussionmentioning

confidence: 90%

Uteroplacental insufficiency alters DNA methylation, one-carbon metabolism, and histone acetylation in IUGR rats

MacLennan

James

Melnyk

et al. 2004

Physiological Genomics

196

139

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. Uteroplacental insufficiency alters DNA methylation, one-carbon metabolism, and histone acetylation in IUGR rats. Physiol Genomics 18: 43-50, 2004. First published April 13, 2004 10.1152/physiolgenomics.00042.2004.-Uteroplacental insufficiency leads to intrauterine growth retardation (IUGR) and increases the risk of insulin resistance and hypertriglyceridemia in both humans and rats. Postnatal changes in hepatic gene expression characterize the postnatal IUGR rat, despite the transient nature of the initial in utero insult. Phenomena such as DNA methylation and histone acetylation can induce a relatively static reprogramming of gene transcription by altering chromatin infrastructure. We therefore hypothesized that uteroplacental insufficiency persistently affects DNA methylation and histone acetylation in the IUGR rat liver. IUGR rat pups were created by inducing uteroplacental insufficiency through bilateral uterine artery ligation of the pregnant dam on day 19 of gestation. The SssI methyltransferase assay and two-dimensional thin-layer chromatography demonstrated genome-wide DNA hypomethylation in postnatal IUGR liver. To investigate a possible mechanism for this hypomethylation, levels of hepatic metabolites and enzyme mRNAs involved in one-carbon metabolism were measured using HPLC with coulometric electrochemical detection and real-time RT-PCR, respectively. Uteroplacental insufficiency increased IUGR levels of S-adenosylhomocysteine, homocysteine, and methionine in association with decreased mRNA levels of methionine adenosyltransferase and cystathionine-␤-synthase. Western blotting further demonstrated that increased quantities of acetylated histone H3 also characterized the IUGR liver. Increased hepatic levels of S-adenosylhomocysteine can promote DNA hypomethylation, which is often associated with histone hyperacetylation. We speculate that the altered intrauterine milieu associated with uteroplacental insufficiency affects hepatic one-carbon metabolism and subsequent DNA methylation, which thereby alters chromatin dynamics and leads to persistent changes in hepatic gene expression.intrauterine growth retardation; one-carbon metabolism; epigenetics; Barker's fetal origins of adult disease hypothesis BARKER'S "fetal origins of adult disease hypothesis" proposes that fetal adaptation to a deprived intrauterine milieu leads to permanent changes in cellular biology and systemic physiology. Intrauterine growth retardation (IUGR) predisposes affected newborns toward long-term morbidity from type 2 diabetes, as well as other components of the metabolic syndrome (2). Uteroplacental insufficiency, a morbidity associated with many common complications of pregnancy such as preeclampsia, induces low ponderal index or asymmetrical IUGR. In the rat, uteroplacental insufficiency induced through bilateral uterine artery ligation of the pregnant dam also results in asymmetrical IUGR and, similar to the human, causes fetal hypoinsulinemia, hypoglycemia, acidosis, and hypoxia (5,14,16,39,40). Juvenile IUGR rats demons...

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Section: Discussionmentioning

confidence: 90%

Uteroplacental insufficiency alters DNA methylation, one-carbon metabolism, and histone acetylation in IUGR rats

MacLennan

James

Melnyk

et al. 2004

Physiological Genomics

196

139

View full text Add to dashboard Cite

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“…Contudo, a associação da desnutrição precoce com o aumento da pressão intra-ocular não foi evidenciado (12) . Baixo peso no primeiro ano de vida tem sido associado com aumento da opacidade cristaliniana, surdez, diminuição de força e alterações dermatológicas (13) . Há evidências que a restrição da dieta instituída em útero ou precocemente após o nascimento pode ter um efeito oposto e está associado com o envelhecimento.…”

Section: Discussão Discussão Discussão Discussão Discussãounclassified

Manifestações oculares em pacientes que tiveram desnutrição nos primeiros seis meses de vida

Dantas¹,

Brandt²,

Leal³

2005

Arq. Bras. Oftalmol.

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“…Low birth weight and shorter birth length were associated with increased mortality risk between 39 and 49 years of age in Danish men [5]. A large-scale cohort study has indicated that in men and women aged 64-74 years, nuclear lens opacities, reduced grip strength and impaired auditory ability were more common in individuals of lower weight at age 1 year, suggesting associations between early life events and the ageing process in humans [6,7].…”

Section: Introductionmentioning

confidence: 99%

The association between birthweight and longevity in the rat is complex and modulated by maternal protein intake during fetal life

Langley‐Evans

Sculley

2006

FEBS Letters

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Maternal protein restriction in rat pregnancy has been suggested to reduce lifespan of the resulting offspring by inducing fetal growth retardation, followed by postnatal catch-up growth. We tested the hypothesis that lifespan could be programmed in both males and females by exposure to undernutrition at specific stages of fetal development. Protein restriction throughout gestation significantly reduced lifespan in both males and females. Low birthweight increased longevity, whilst rapid postnatal growth had a detrimental effect. There was no evidence that undernutrition programmed lifespan through oxidative processes in the major organs. Fetal programming is an important contributor to the ageing process.

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Are rates of ageing determined in utero?

Abstract: the associations between early growth and markers of ageing suggest that in some systems, ageing may be programmed by events in early life. A potential mechanism is the impaired development of repair systems.

Cited by 146 publications

References 13 publications

Uteroplacental insufficiency alters DNA methylation, one-carbon metabolism, and histone acetylation in IUGR rats

Uteroplacental insufficiency alters DNA methylation, one-carbon metabolism, and histone acetylation in IUGR rats

Manifestações oculares em pacientes que tiveram desnutrição nos primeiros seis meses de vida

The association between birthweight and longevity in the rat is complex and modulated by maternal protein intake during fetal life

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