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SA-β-Galactosidase-Based Screening Assay for the Identification of Senotherapeutic Drugs
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Early growth and ageing
J-H Chen1, E C Cottrell, S E Ozanne
1Institute of Metabolic Science, Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Abstract:
Effects of in utero and early life conditions on adult health and disease such as cardiovascular disease and type 2 diabetes are well documented by epidemiological and clinical observations. Animal models including intrauterine artery ligation, maternal restriction of iron, protein or general caloric intake, provide invaluable tools to understand mechanisms linking early growth and later diseases in adult life. In addition, the rodent model of maternal protein restriction has revealed that longevity can be influenced either positively or negatively by early growth patterns. Recent rapid advances in the ageing field using model organisms involving caloric restriction and genetic mutation as well as gene overexpression demonstrated the importance of insulin/ IGF-1 signaling pathways, oxidative damage and SIRT1 in the regulation of lifespan. Studies using rodent models of maternal protein restriction suggest that alteration in insulin metabolism, changes in expression of antioxidant defense systems and in levels of oxidative damage (including telomere attrition) may also play a key role in regulation of lifespan by the early environment. It is suggested that neuroendocrine systems and epigenetic modification may be the potential mechanisms underlying beneficial or detrimental effects of early growth on the regulation of lifespan. Further studies in this area are warranted.
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