CARC RC3: ALCOHOL USE DISORDER AND AGING IN HIV: THE ROLE OF THE MICROBIOTA & INFLAMM-AGING Excessive alcohol use contributes to the pathogenesis of a variety of geriatric medical conditions. Hypertension, heart failure, diabetes, chronic obstructive pulmonary disease, osteoporosis and cognitive impairment all occur at the intersection between Alcohol Use Disorder (AUD) and old age. Less appreciated is the connection between AUD and biological aging although some data suggests that harmful alcohol intake leads to precocious aging at the cellular level. Similarly, Human Immunodeficiency Virus (HIV) infection appears to accelerate the aging process. Chronologically young HIV+ persons are afflicted with many of the same geriatric aliments common to advanced age including the geriatric frailty syndrome and increases in senescent immune cells. Given these findings, an enhanced understanding of contributing factors and underlying mechanisms resulting in accelerated aging in HIV represents a critical public health concern. It is currently unknown whether or not AUD in HIV-infected patients hastens biological aging and what mechanisms may be involved. We propose a model of alcohol-induced aging by which HIV and AUD interact to accelerate the rate of aging through their overlapping effects on the gastrointestinal tract microbiota, which, in turn, perpetuates a chronic pro-inflammatory state. This Research Component proposes the overarching hypothesis that excessive alcohol use in HIV-infected individuals accelerates aging. We further hypothesize that alimentary tract dysbiosis in HIV-infected individuals with alcohol use disorder accelerates aging by amplifying inflamm-aging. These hypotheses will be tested through the conduct of a longitudinal cohort study of HIV+ patients in New Orleans. Three Objectives will be achieved during the course of this study: (1) To determine the effects of AUD on the alimentary tract microbiota in HIV- infected individuals. The hypothesis that AUD reduces microbial community diversity and alters taxonomic membership will be tested by phylogenetic analysis of ribosomal DNA sequences from oral and stool samples. (2) To resolve the roles of AUD & the microbiota in escalating inflamm-aging in HIV+ patients. This will test the hypothesis that harmful alcohol use results in immune activation and senescence through assays characterizing blood cell phenotypes and function. (3) To assess the influence of AUD, the microbiota & inflamm-aging on biological age in HIV. A multidimensional Profile of Aging will be used to test the hypothesis that AUD and/or the microbiota and/or inflamm-aging accelerate biological aging in people living with HIV / AIDS. The knowledge gained from this study has significant potential to identify novel therapeutic targets for the treatment of AUD-induced frailty and geriatric medical conditions in HIV seropositive patients.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Comprehensive Center (P60)
Project #
5P60AA009803-24
Application #
9182852
Study Section
Special Emphasis Panel (ZAA1)
Project Start
Project End
Budget Start
2016-12-01
Budget End
2017-11-30
Support Year
24
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Louisiana State Univ Hsc New Orleans
Department
Type
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
Merrill, Livia C; Jones, Christopher W; Drury, Stacy S et al. (2017) The differential impact of oxytocin receptor gene in violence-exposed boys and girls. Int J Dev Neurosci 59:60-67
Byerley, Lauri O; Samuelson, Derrick; Blanchard 4th, Eugene et al. (2017) Changes in the gut microbial communities following addition of walnuts to the diet. J Nutr Biochem 48:94-102
Ruan, Sanbao; Cai, Yang; Ramsay, Alistair J et al. (2017) B cell and antibody responses in mice induced by a putative cell surface peptidase of Pneumocystis murina protect against experimental infection. Vaccine 35:672-679
Samuelson, Derrick R; Shellito, Judd E; Maffei, Vincent J et al. (2017) Alcohol-associated intestinal dysbiosis impairs pulmonary host defense against Klebsiella pneumoniae. PLoS Pathog 13:e1006426
Ng, Hang Pong; Jennings, Scott; Wang, Jack et al. (2017) Non-canonical Glucocorticoid Receptor Transactivation of gilz by Alcohol Suppresses Cell Inflammatory Response. Front Immunol 8:661
Duplanty, Anthony A; Simon, Liz; Molina, Patricia E (2017) Chronic Binge Alcohol-Induced Dysregulation of Mitochondrial-Related Genes in Skeletal Muscle of Simian Immunodeficiency Virus-Infected Rhesus Macaques at End-Stage Disease. Alcohol Alcohol 52:298-304
Simon, Liz; Siggins, Robert; Winsauer, Peter et al. (2017) Simian Immunodeficiency Virus Infection Increases Blood Ethanol Concentration Duration After Both Acute and Chronic Administration. AIDS Res Hum Retroviruses :
Goldsmith, Felicia; Guice, Justin; Page, Ryan et al. (2017) Obese ZDF rats fermented resistant starch with effects on gut microbiota but no reduction in abdominal fat. Mol Nutr Food Res 61:
Theall, Katherine P; Shirtcliff, Elizabeth A; Dismukes, Andrew R et al. (2017) Association Between Neighborhood Violence and Biological Stress in Children. JAMA Pediatr 171:53-60
Felker-Kantor, Erica; Wallace, Maeve; Theall, Katherine (2017) Living in violence: Neighborhood domestic violence and small for gestational age births. Health Place 46:130-136

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