Longevity is impacted by growth hormone action during early postnatal period

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.DOI: http://dx.doi.org/10.7554/eLife.24059.001

Lifespan of long‐lived growth hormone receptor knockout mice was not normalized by housing at 30°C since weaning

“…We do not currently understand the precise mechanism for this discrepancy, but believe that the most likely explanation is the difference in the age of the animals at the time of transferring them from 23°C to 30°C. The suggested importance of exposing juvenile versus adult mice to increased eT is consistent with the well‐documented potential of early life nutritional, hormonal, or environmental interventions to influence adult phenotypic characteristics, including rate of aging and longevity (Barker, ; Bartke & Quainoo, ; Sun et al,). The data generated in adult Ames dwarf mice concerning energy metabolism (Darcy et al, ) are likely influenced by profound suppression of thyroid function in these animals.…”

MECHANISMS IN ENDOCRINOLOGY: Lessons from growth hormone receptor gene-disrupted mice: are there benefits of endocrine defects?

“…(ii) Bartke and colleagues, have dealt intensively into various conditions of GH deficit and ageing (198,242) and recently reported that a short (6 weeks) phase of early exposure to GH (starting at 2 weeks age) reduced lifespan and cellular stress resistance in Ames dwarf mice (243). A parallel thyroxine treatment had no effect on lifespan (243,244,245) whereas thyroxine and GH combined treatment reduced maximal lifespan in only female Ames mice (246). (iii) Extensive work by Brown-Borg and colleagues have described epigenetic signatures in DNA methylation patterns in Ames mice compared to their WT littermates (247,248).…”

“…Interestingly, while considering the detrimental effect of lack of GH in GHD patients, an important point to consider is that GHD patients did not have a congenital absence of GH action, but rather had a peri-and post-natal exposure to GH, prior to development of GHD. As recent research indicates, an early life GH treatment in fact decreases lifespan and adversely affects the inflammatory profiles in liver and adipose tissue of the long-lived GHD Ames mice (243,244). Additionally, high endogenous GH levels in children born very preterm was associated with a reduced spatial memory and an enlarged amygdala(294) Together, the currently available information from humans and mice indicate an improvement in memory and cognition associated with congenital absence of GH action as well as with GH treatment in some cases of GH deficiency.…”

Sex differences in the response to dietary restriction in rodents

“…Interestingly, pathways implicated in longevity have been shown to exhibit sexual dimorphism such as the nutrient-responsive mTOR [9], the Sirtuins (particularly SIRT-6) [10], IGF-1 [11], and growth hormone [12,13]. …”