Aging and Oxidative Stress Influence Salivary Gland Disease in Sjogren's Syndrome

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

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Principal Investigator: Umesh S Deshmukh
Organization: OKLAHOMA MEDICAL RESEARCH FOUNDATION
Fiscal Year: 2024
Award: $500,954
Funding agency: National Institute of Dental and Craniofacial Research

Sjögren’s Syndrome (SS) is a chronic and debilitating systemic autoimmune disorder afflicting multiple
organ systems. The targeting of the exocrine salivary and lacrimal glands by an autoimmune and
inflammatory response leads to organ dysfunction causing reduced fluid secretion, which manifests
into the dry mouth and dry eye symptoms of the disorder. Although a wide age range is reported in
patients at diagnosis, it is well known that most SS patients are older. Why phenotypic traits are more
prominent in older patients is unknown. Aging organs show heightened oxidative stress, which is often
associated with declining organ function. Although,. SS patients show evidence of increased oxidative
stress markers; whether elevated oxidative stress is causative or the outcome of an inflammatory
response is unclear and challenging to investigate in patients. Hence based on published literature and
our preliminary data, this proposal will test the overall hypothesis that the combined effects of
autoimmunity and aging-associated oxidative stress contribute to salivary gland disease and
dysfunction in SS. Aim 1 of this proposal will specifically address the hypothesis that aging-associated
oxidative stress makes salivary glands more susceptible to immune-mediated damage. And in aim 2,
by using a novel mouse model system, we will test the hypothesis that oxidative stress per se in salivary
gland epithelial cells is insufficient to cause SS. The primary goal of this proposal is to understand the
mechanisms behind key clinical observations in SS patients: prominence of clinical symptoms at an
older age and the possible role of elevated oxidative stress in the disease process. Understanding
basic mechanisms linking aging with organ dysfunction in SS will be essential in developing novel
modalities to treat the disease.

Terms: <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><Address><Affect><Age><Aged 65 and Over><Aging><Animal Model><Animal Models and Related Studies><Antibodies><Appearance><Asialia><Autoantibodies><Autoantigens><Autoimmune Diseases><Autoimmune Responses><Autoimmune Status><Autoimmunity><Autologous Antigens><Big Data><BigData><Biologic Models><Biological Models><Body System><Body Tissues><Cell Body><Cells><Cellular injury><Chronic><Circulation><Clinical><Color><Complement><Complement Proteins><Complex><Conjunctival Epithelium><Country><Data><Development><Diagnosis><Disease><Disorder><Disproportionate number of females><Disproportionate number of women><Disproportionately affects females><Disproportionately affects women><Disproportionately impacts females><Disproportionately impacts women><Disproportionately in females><Disproportionately in women><Dryness><Ductal Cell><Ductal Epithelial Cell><Dysfunction><Enzyme Gene><Enzymes><Epithelial Cells><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Fluids and Secretions><Free Radicals><Frequencies><Functional disorder><Genetic><Genetic Predisposition><Genetic Predisposition to Disease><Genetic Susceptibility><Genetic propensity><Gland><Goals><Hyperactivity><Hyposalivation><IPO-B><Immune><Immune response><Immune system><Immunes><Immunological response><Indophenol Oxidase B><Inflammatory Response><Inherited Predisposition><Inherited Susceptibility><Injury><KO mice><Knock-out Mice><Knockout Mice><Lacrimal Glands><Lacrimal gland structure><Link><Literature><Location><MNSOD><Macrophage><Manganese Superoxide Dismutase><Mediating><Mice><Mice Mammals><Mitochondria><Mitochondrial Superoxide Dismutase><Mn Superoxide Dismutase><Mn-SOD><Modality><Model System><Modeling><Mouth Dryness><Murine><Mus><Mφ><Null Mouse><Older Population><Oral><Organ><Organ System><Outcome><Oxidative Stress><Oxidative Stress Induction><Pathway interactions><Patients><Phenotype><Physiopathology><Population><Predisposition><Process><Production><Proteomics><Publishing><Recovery><Reporting><Respiration><Risk Factors><Role><SOD2><SOD2 gene><Saliva><Salivary Gland Diseases><Salivary Glands><Salivary Glands Head and Neck><Self-Antigens><Sialadenitis><Sialoadenitis><Sicca Syndrome><Sjogren's Syndrome><Sjogrens><Sjögren Syndrome><Superoxide Anion><Superoxide Dismutase 2><Superoxide Radical><Superoxides><Susceptibility><Symptoms><Testing><Tissues><Work><Xerostomia><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 ≥65><ages><aging associated><aging related><alleviate symptom><ameliorating symptom><aptyalism><autoimmune antibody><autoimmune condition><autoimmune disorder><autoimmunity disease><autoreactive antibody><cell damage><cell injury><cellular damage><complementation><damage to cells><decrease symptom><developmental><digital><dry eye><dry mouth><elderly patient><expectation><eye dryness><female bias><female preponderance><fewer symptoms><flow cytophotometry><genetic etiology><genetic mechanism of disease><genetic vulnerability><genetically predisposed><host response><human old age (65+)><immune system response><immunoresponse><in vivo><injuries><injury to cells><innovate><innovation><innovative><mitochondrial><model of animal><mouse model><murine model><new therapeutic approach><new therapeutic intervention><new therapeutic strategies><new therapy approaches><new treatment approach><new treatment strategy><novel><novel therapeutic approach><novel therapeutic intervention><novel therapeutic strategies><novel therapy approach><old age><older groups><older individuals><older patient><older person><over 65 years><pathophysiology><pathway><reduce symptoms><relieves symptoms><respiratory mechanism><salivary disorder><salivary gland disorder><salivary gland inflammation><self reactive antibody><sex><social role><symptom alleviation><symptom reduction><symptom relief><symptom treatment><symptomatic treatment><systemic autoimmune disease><systemic autoimmune disorder><tool><trait><treat symptom><women's preponderance><xerodermosteosis><≥65 years>