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.
Showing the most recent 10 out of 114 publications
