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Principal Investigator: Rebecca Mountain
Organization: MAINEHEALTH
Fiscal Year: 2024
Award: $127,427
Funding agency: National Institute of Arthritis and Musculoskeletal and Skin Diseases
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.
Terms: <11-Hydroxysteroid Dehydrogenase><11-beta-Hydroxysteroid Dehydrogenases><11B-Hydroxysteroid Dehydrogenase><11beta-Hydroxysteroid Dehydrogenase><2-methyl-1,2-di-3-pyridinyl-1-propanone><65 and older><65 or older><65 years of age and older><65 years of age or more><65 years of age or older><65+ years><65+ years old><> 65 years><Adrenergic Agents><Adrenergic Drugs><Adrenergics><Affect><Aged 65 and Over><Anxiety><Architecture><Autoregulation><Biological Markers><Blood Serum><Bone Density><Bone Formation><Bone Marrow><Bone Marrow Reticuloendothelial System><Bone Mineral Density><Bone Resorption><Brain><Brain Nervous System><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 years><Cancellous bone><Catecholamine Receptor><Catecholamines><Cell Communication and Signaling><Cell Signaling><Clinical><Clinical Research><Clinical Study><Clinical Treatment><Complex I Dehydrogenase><Corticosteroid 11-Oxidoreductase><Corticosteroid 11-Reductase><Corticosterone><Cortisone 11-Oxoreductase><Data><Differences between sexes><Differs between sexes><Disease><Disorder><Electron Transport Complex I><Encephalon><Engineering / Architecture><Epidemiologic Research><Epidemiologic Studies><Epidemiological Studies><Epidemiology Research><Exposure to><Female><Femur><Fracture><Future><Gene Expression><Genes><Genetic><Glucocorticoid Receptor><Glucocorticoids><Goals><Groups at risk><Health><Histologic><Histologically><Homeostasis><Human><Image><Individual><Intermediary Metabolism><Intracellular Communication and Signaling><KO mice><Knock-out Mice><Knockout Mice><Loneliness><Long-Term Effects><Longterm Effects><Measures><Mediating><Mental Depression><Mental Health><Mental Hygiene><Mental disorders><Mental health disorders><Metabolic><Metabolic Processes><Metabolism><Methbipyranone><Methopyrapone><Metyrapone><Mice><Mice Mammals><Micro RNA><MicroRNA Expression Profiling><MicroRNAs><Modeling><Modern Man><Molecular><Morbidity><Morbidity - disease rate><Murine><Mus><NADH DH I><NADH Dehydrogenase Complex 1><NADH Dehydrogenase I><NADH Q1 Oxidoreductase><NADH dehydrogenase (ubiquinone)><NADH-CoQ Reductase><NADH-Coenzyme Q Reductase><NADH-Ubiquinone Oxidoreductase><NADH-Ubiquinone Reductase><Null Mouse><Osteoclastic Bone Loss><Osteogenesis><Osteoporosis><Outcome><People at risk><Persons at risk><Phase><Phenotype><Physiologic><Physiological><Physiological Homeostasis><Populations at Risk><Prevalence><Preventative strategy><Prevention strategy><Preventive strategy><Propanolol><Propranolol><Proteomics><Psyche structure><Psychiatric Disease><Psychiatric Disorder><Psychological Health><Psychosocial Stress><Public Health><Receptor Protein><Research><Respiratory Complex I><Risk><Rodent><Rodentia><Rodents Mammals><Role><Rotenone-Sensitive Mitochondrial NADH-Ubiquinone Oxidoreductase><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><Serum><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Sex Differences><Sexual differences><Signal Transduction><Signal Transduction Systems><Signaling><Social isolation><Stress><Sympathetic Nervous System><Sympathins><Testing><Thick><Thickness><Time><Ubiquinone Reductase><Work><above age 65><after age 65><age 65 and greater><age 65 and older><age 65 or older><age > 65><age of 65 years onward><aged 65 and greater><aged 65+><aged mice><aged mouse><aged ≥65><antagonism><antagonist><beta-2 Adrenergic Receptors><bio-markers><biologic marker><biological sex><biological signal transduction><biomarker><bone><bone fracture><bone health><bone loss><bone mass><bone metabolism><bone tissue formation><circulating miRNA><circulating miRNAs><circulating microRNA><circulating microRNAs><complex 1 dehydrogenase><coping><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><death risk><depression><elderly mice><epidemiologic investigation><epidemiology study><experience><fracture risk><genetic approach><genetic strategy><global miRNA profiling><human old age (65+)><imaging><inhibitor><isolated individuals><isolated people><lonely><lonely individuals><lonely people><male><mental><mental illness><miRNA><miRNA expression profiling><miRNA sequencing><miRNA-seq><miRNAs><micro RNA expression profiling><microRNA profiling><microRNA sequencing><mortality><mortality risk><mouse model><murine model><neural><novel><old age><old mice><older adult><older adulthood><over 65 years><pharmacologic><prevent><preventing><psychiatric illness><psychological disorder><receptor><receptor expression><response><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><sex><sex based differences><sex-dependent differences><sex-related differences><sex-specific differences><skeletal><social role><stress disorder><substantia spongiosa><substantia trabecularis><therapeutic target><trabecular bone><treatment strategy><trial regimen><trial treatment><type 1 dehydrogenase><β-2 Adrenoceptor><β2 Adrenergic Receptor><≥65 years>