Brain Structure and Function Associated with Younger Adults in Growth Hormone Receptor-Deficient Humans

Abstract

Growth hormone receptor deficiency (GHRD) results in short stature, enhanced insulin sensitivity, and low circulating levels of insulin and insulin-like growth factor 1 (IGF-1). Previous studies in mice and humans suggested that GHRD has protective effects against age-related diseases, including cancer and diabetes. Whereas GHRD mice show improved age-dependent cognitive performance, the effect of GHRD on human cognition remains unknown. Using MRI, we compared brain structure, function, and connectivity between 13 people with GHRD and 12 unaffected relatives. We assessed differences in white matter microstructural integrity, hippocampal volume, subregional volumes, and cortical thickness and surface area of selected regions. We also evaluated brain activity at rest and during a hippocampal-dependent pattern separation task. The GHRD group had larger surface areas in several frontal and cingulate regions and showed trends toward larger dentategyrusandCA1regionsofthehippocampus.Theyhadlowermeandiffusivityinthegenuofthecorpuscallosumandtheanteriorthalamic tracts. The GHRD group showed enhanced cognitive performance and greater task-related activation in frontal, parietal, and hippocampal regions compared with controls. Furthermore, they had greater functional synchronicity of activity between the precuneus and the rest of the default mode network at rest. The results suggest that, compared with controls, GHRD subjects have brain structure and function that are more consistent with those observed in younger adults reported in previous studies. Further investigation may lead to improved understanding of underlying mechanisms and could contribute to the identification of treatments for age-related cognitive deficits.

The physiology of endocrine systems with ageing

“…32 Although the age-related decline in the activity of the growth hormone-IGF-1 axis is considered to contribute to age-related changes that are similar to those observed in growth hormone-deficient adults, growth hormone–IGF-1 deficiency or resistance is also known to result in prolonged life expectancy, at least in animals. 33–35 These data raise the question of whether or not growth hormone deficiency constitutes a beneficial adaptation to ageing, and therefore requires no therapy. Moreover, although growth hormone therapy has been shown to exert positive effects on growth hormone-deficient patients, its safety, efficacy, and role in healthy older individuals is highly controversial.…”

“…33 Further investigation could lead to an improved understanding of the mechanisms underlying these differences in brain structure and function, and could contribute to the identification of treatments for age-related cognitive deficits. This observation raises the possibility that growth hormone receptor inhibition has the potential to protect against age-dependent cognitive decline.…”

“…This observation raises the possibility that growth hormone receptor inhibition has the potential to protect against age-dependent cognitive decline. 33 …”

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

“…However, recently a small study with 12 members of the Ecuadorian cohort of LS patients reported that they performed significantly better in memory tasks and had significantly lower cognitive impairment compared to their unaffected relatives (273). In human acromegaly patients, recent studies have reported cognition deficits, decreased short-term and long-term memory, anxiety and impaired decision making, and decreased activities in pre-frontal and mid-temporal cortices in brain (274,275,276,277).…”

Spirulina Enhances Bone Modeling in Growing Male Rats by Regulating Growth-Related Hormones

“…The height of children is rapidly becoming a social issue as there is an increase in the number of people who are concerned about their child's height. As a result, GH therapy is being indiscriminately used without adequate protection against side effects [38][39][40][41][42][43][44][45][46][47]. This study investigated the beneficial effect of using spirulina as a dietary supplement on skeletal growth and growth-related hormone levels in growing male rats.…”