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Title: Effect of maternal protein restriction upon growth, longevity and telomere shortening
Author: Jennings, B.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1999
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Life expectancy is often determined by cardiovascular disease, cancer, stroke, and diabetes which become increasingly prevalent with age. Epidemiological studies have revealed links between birth weight and the subsequent development of those diseases. Animal studies have implicated poor fetal nutrition in causing adaptations to the development of disease. The work described in this thesis examined the effects of protein restriction during different periods of development on subsequent growth and longevity. It was established that it was not the duration of protein restriction but the timing of dietary manipulation which was essential for regulating growth. Protein restriction during lactation was found to programme appetite and gave rise to permanently slower growth rates but increased longevity. In contrast growth restriction caused by maternal protein deprivation during fetal life followed by rapid catch-up growth was associated with reduced survival. Telomeres are thought to play a role in cellular ageing and senescence. Therefore the possibility that the observed differences in longevity were related to changes in telomere length was investigated. Age-related shortening of telomeres was detected in the liver and kidney of control male rats. Brain telomere lengths remained relatively constant throughout life. Kidney telomere lengths were significantly shorter in 13 month old male rats who had been growth retarded during fetal life and then experienced rapid catch-up growth compared to rats who were growth retarded during lactation. No such differences were observed in the liver or brain. In summary this thesis demonstrates that protein restriction during fetal life, followed by catch-up growth resulted in decreased longevity associated with increased telomere shortening in the kidney. In contrast protein restriction during lactation permanently reduced the rate of growth and the rate of telomere shortening but prolonged longevity. This may provide a mechanistic basis for epidemiological studies linking early growth retardation to adult degenerative diseases.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available