CORRECTING GLUTATHIONE DEFICIENCY REVERSES MITOCHONDRIAL DYSFUNCTION AND ACCELERATED AGING IN PATIENTS WITH HIV

Abstract Patients with HIV (PWH) have ‘accelerated’ aging based on early manifestation of geriatric comorbidities of declining physical-function, elevated inflammation, insulin-resistance, cognitive-impairment and abdominal-obesity, but contributing mechanisms are not well understood and interventions are lacking. We hypothesized that deficiency of the intracellular-antioxidant Glutathione results in impaired mitochondrial fuel-oxidation (MFO) and contributes to these defects, and that supplementing Glutathione precursors glycine and N-acetylcysteine (GlyNAC) could improve these defects. In an open-label trial, 8 PWH were studied before and after 12-weeks of GlyNAC supplementation (and 8-weeks after stopping GlyNAC), and compared to 8 matched, unsupplemented, uninfected controls. PWH had significantly impaired MFO, abnormal molecular regulation of MFO, muscle Glutathione deficiency, physical decline, cognitive-impairment, and higher oxidative-stress, inflammation, insulin-resistance and total body fat. GlyNAC supplementation significantly improved these defects, but benefits receded on stopping GlyNAC. These data suggest that GlyNAC supplementation could reverse ‘accelerated aging’ in PWH by improving defects linked to impaired MFO.


ENERGY EXPENDITURE AND PHYSICAL ACTIVITY AMONG OLDER PARTICIPANTS FROM THE MULTICENTER AIDS COHORT STUDY (MACS)
Jennifer A. Schrack, 1 Todd T. Brown, 2 and Joseph B. Margolick 3 , 1. Johns Hopkins University, Baltimore,Maryland,United States,2. Johns Hopkins Medical Institutions,Baltimore,Maryland,United States,3. Johns Hopkins Bloomberg School of Public Health,Baltimore,Maryland,United States Energy utilization becomes more inefficient with age and is linked to low physical activity and functional decline. Persons aging with HIV exhibit accelerated functional decline, but the effect of chronic HIV infection on energy utilization and free-living physical activity remains unclear. We investigated cross-sectional associations between age and: resting metabolic rate, peak walking energy (VO2), and 7-day physical activity by accelerometry in 100 men in the MACS (age: 60.8+/-6.8 years, 35% black, 46.1% HIV+, 94% virally suppressed). In multivariable regression models adjusted for age, BMI, race, chronic conditions, and HIV viral load, HIV+ men had a higher resting metabolic rate (β=103.2 kcals/day, p=0.03) and lower peak walking VO2 (β=-1.8 ml/kg/min, p<0.02) than HIV-men. Moreover, HIV+ men demonstrated lower physical activity, overall and by time of day (p<0.05). These results suggest that energy utilization differs by HIV serostatus, which may contribute to lower physical activity and function with aging.

FUNCTIONAL WELLNESS AND OLDER MEN WITH HIV
Tonya N. Taylor, 1 Jeremy Weedon, 1 and Tarik Silk 1 , 1.

SUNY Downstate Medical Center, Brooklyn, New York, United States
Aging-related stressors, such as changing physical function, poorly managed multimorbidity, increasing pill burden and social losses can diminish for some older adults with HIV the capacity for self-care. These challenges, however, can be improved by maintaining physical, cognitive and social function, or functional wellness. Using cross-sectional data from a men's health study with younger and older men with and without HIV, we conducted general linear models to identify individual and clinical predictors for physical, cognitive, social and role function, as measured by the Medical Outcomes Study HIV Health Survey. We found that older HIV+ men had lower burdens of functional deficits compared to older HIV-men and younger HIV+ men and that across all models, depression, followed by diabetes, housing, and employment were predictive of functional wellness. Functional wellness for older HIV+ men is a multidimensional construct that includes optimizing internal and external resources to maintain healthy living and wellness.

. Baylor College of Medicine, Houston, Texas, United States
Patients with HIV (PWH) have 'accelerated' aging based on early manifestation of geriatric comorbidities of declining physical-function, elevated inflammation, insulin-resistance, cognitive-impairment and abdominal-obesity, but contributing mechanisms are not well understood and interventions are lacking. We hypothesized that deficiency of the intracellular-antioxidant Glutathione results in impaired mitochondrial fuel-oxidation (MFO) and contributes to these defects, and that supplementing Glutathione precursors glycine and N-acetylcysteine (GlyNAC) could improve these defects. In an open-label trial, 8 PWH were studied before and after 12-weeks of GlyNAC supplementation (and 8-weeks after stopping GlyNAC), and compared to 8 matched, unsupplemented, uninfected controls. PWH had significantly impaired MFO, abnormal molecular regulation of MFO, muscle Glutathione deficiency, physical decline, cognitiveimpairment, and higher oxidative-stress, inflammation, insulin-resistance and total body fat. GlyNAC supplementation significantly improved these defects, but benefits receded on stopping GlyNAC. These data suggest that GlyNAC supplementation could reverse 'accelerated aging' in PWH by improving defects linked to impaired MFO.

SESSION 2490 (SYMPOSIUM)
HOME IS WHERE THE HEART IS: OPTIMIZING AND TAILORING HOME AND COMMUNITY-BASED SUPPORT FOR DEMENTIA CAREGIVERS Chair: Quincy M. Samus, The Johns Hopkins University, Baltimore, Maryland, United States Innovation in Aging, 2019, Vol. 3, No. S1