Abstract
Life-long lack of growth hormone (GH) action can produce remarkable extension of longevity in mice. Here we report that GH treatment limited to a few weeks during development influences the lifespan of long-lived Ames dwarf and normal littermate control mice in a genotype and sex-specific manner. Studies in a separate cohort of Ames dwarf mice show that this short period of the GH exposure during early development produces persistent phenotypic, metabolic and molecular changes that are evident in late adult life. These effects may represent mechanisms responsible for reduced longevity of dwarf mice exposed to GH treatment early in life. Our data suggest that developmental programming of aging importantly contributes to (and perhaps explains) the well documented developmental origins of adult disease.
Highlights
Epidemiological studies of individuals born or conceived during the ‘Dutch famine’ led to an appreciation of the impact of early-life events on adult health, and this important concept was formalized as the ‘Barker hypothesis’ (Barker, 1997)
Decreased lifespan in ames dwarf mice by transient exposure to growth hormone (GH) during early To evaluate the effect of early-life GH treatment on longevity, we examined the survival of Ames dwarf (Prop1df/df) mice and normal littermate control mice employing two treatment protocols in which GH or vehicle was administered starting at the first or second postnatal weeks
Analysis of each sex separately showed that median lifespan in male Prop1df/df mice was shortened by 204 days (20%; from 1011 to 807 days) by GH treatment between postnatal first and seventh week (Figure 1B,C), with the overall survival being significantly decreased (p=0.008)
Summary
Epidemiological studies of individuals born or conceived during the ‘Dutch famine’ led to an appreciation of the impact of early-life events on adult health, and this important concept was formalized as the ‘Barker hypothesis’ (Barker, 1997). Recent studies have shown that maternal overnutrition and obesity are strongly associated with adult metabolic dysfunction in the offspring (Curhan et al, 1996; Levin and Govek, 1998). This evidence linked early growth status and nutrient signals to the development of diseases in adult life, and this concept has been formulated as the Developmental Origins of Health and Diseases (Hanson and Gluckman, 2014; Sinclair et al, 2007). Moderate reduction of food or protein intake during pregnancy of female rats and mice lead to improved metabolic status and extended longevity
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