Investigating the Impact of Social Isolation on Bone Metabolism

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PROJECT SUMMARY Social isolation is a potent form of psychosocial stress, and a growing public health concern. Older adults, particularly those individuals isolated during the COVID-19 pandemic, are particularly vulnerable. One in four individuals over the age of 65 are estimated to be affected by social isolation and loneliness, which are associated with an increase in mortality risk by up to 70%. Previous studies have shown other forms of psychosocial stress and mental illness are associated with increased risk for osteoporosis and related fractures, which are likewise associated with increased mortality in older adults. Despite the increase in social isolation and the overlap between at-risk populations, there has been little research on the effects of social isolation on bone loss and skeletal metabolism. The limited work that has been done in rodents suggest that social isolation negatively impacts bone health, leading to decreased bone mineral density. None of these studies, however, have explored the mechanisms of isolation-induced bone loss, or examined differences in the effect of isolation on bone between the sexes. My own preliminary studies show that males exposed to social isolation had reduced femoral bone volume fraction, bone mineral density, and cortical thickness. Females, conversely, did not have any reduction in bone mass. My data also showed changes to glucocorticoid receptor and β2 adrenergic receptor expression as a result of social isolation, which both have known effects on bone. The goal of this project is therefore to test the overarching hypothesis that social isolation leads to bone loss through altered glucocorticoid (Aim 1) and sympathetic nervous system (Aim 2) activity. I will test these hypotheses using a 4 to 8-week-long mouse model of social isolation in 16-week old mice, in combination of pharmacological and genetic approaches. I will also use proteomic and microRNA sequencing approaches to identify novel systemic changes in response to social isolation that may impact bone. The proposed project will be the first study to identify mediating mechanisms of social isolation-induced bone loss and precisely test the effects of isolation on bone metabolism through a range of imaging, genetic, histologic, and omic approaches. The results of this project will inform future clinical and epidemiological studies, and help identify prevention strategies and treatments for individuals at the greatest risk for social isolation.