FLAVIN-CONTAINING MONOOXYGENASES (FMOS): LONGEVITY-PROMOTING ENZYMES OR ATHEROSCLEROSIS RISK FACTOR?

Abstract Since their discovery in 1970, flavin-containing monooxygenases (FMOs) have been studied as Phase 1 xenobiotic metabolizing enzymes that act on sulfur- and nitrogen-containing small molecules. In 2015, we demonstrated that C. elegans (worm) fmo-2 was not only necessary for hypoxic response and dietary restriction-mediated lifespan extension, but was also sufficient to extend lifespan when overexpressed. Consistenet with a conserved role for FMOs as longevity-promoting enzymes, mouse hepatic Fmo3 transcript is highly upregulated by numerous major lifespan extending interventions. A contrasting series of reports, however, have described mammalian Fmo3-mediated production of trimethylamine N-oxide (TMAO) as a risk factor for atherosclerosis and other major diseases. My thesis research aims to define the regulation and function of worm fmo-2 using genetic and biochemical approaches. My data thus far support the hypothesis that fmo-2 acts on sulfur amino acid pathway intermediates to promote longevity and healthspan.

end-of-life decisions as a surrogate is especially challenging. Notably, few evidence-based interventions exist to support caregivers in this capacity. Guided by the Ottawa Decision Support Framework which recognizes three determinants of informed decisions -information, value clarity, and support, the current study identifies key value considerations and information needs among family caregivers as they weigh decisions regarding hospice enrollment and artificial nutrition and hydration (AHN) for PWDs. One focus group (n=7) and four individual interviews (n=4) were conducted with dementia family caregivers. All face-to-face and telephone interviews were audio-recorded, transcribed verbatim, and verified for accuracy. Thematic analysis (Braun & Clarke, 2006) was conducted to identify and organize themes. Two main themes and subthemes emerged: 1. Caregivers expressed hospice-related values including having enough knowledge about hospice treatments for both Alzheimer's and new symptoms, having caregiver support services, considering family needs, and weighing the extent the PWD can engage with others meaningfully and remain at home. 2. Caregivers shared AHN-related values including clearly understanding AHN treatments, services and risks for the PWD considering the patient's functional status. Participants' information needs reflected their priority of practical needs being met. These findings offer implications for how to design decision support tools and interventions that provide practical and specific information on the benefits and risks of hospice and AHN for PWDs and caregivers.

SOCIAL DETERMINANTS OF HEALTH DRIVE EMERGENCY ROOM AND HOSPITAL USE BY DUAL ELIGIBLE AND DISABLED PENNSYLVANIANS
Sih-Ting Cai, 1 Howard Degenholtz, 1 and Hayley Germack 1 ,

University of Pittsburgh, Pittsburgh, Pennsylvania, United States
The study examined correlates and consequences of social determinants of health risk factors (SDoH) among dual eligible aged and disabled individuals; Pennsylvania is transitioning this population into a managed care plan with responsibility for care coordination and incentives to prevent hospitalization and nursing home placement. Medicaid and Medicare claims were used to identify people with SDoH based on ICD-10 codes in 2016 in four domains: economic insecurity, life stressors, physical dependence, and potential health hazards. Of 281,918 people, 38.6% had one or more SDoH. Among people with severe mental illnesses (SMI; schizophrenia, psychosis, major depressive disorder, or bipolar disorder), the prevalence of SDoH was 57.9%. Of people with one or more SDoH, 42% visited the ED, compared to only 32% of people with no SDoH. Economic insecurity (OR 1.68; CI 1.59-1.78), life stressors (OR 1.39; CI 1.29-1.48), physical dependence, (OR 2.01; CI 1.97-2.06), and potential health hazards (OR 1.52; CI 1.47-1.56) were independently associated with risk of hospitalization, controlling for age, gender, race, SMI, chronic conditions and disability. The introduction of diagnosis codes for SDoH under ICD-10 has facilitated identifying individuals with deficits that might increase health care use above and beyond their underlying health status. Although the prevalence of these risk factors as captured in diagnosis data is likely an underestimate, the strong association with subsequent ED use and hospitalization lends credence to these indicators. Medicare and Medicaid claims data can be used to identify people with SDoH and target interventions to prevent downstream health services use.

UNIQUE TRANSCRIPTOME OF AGE-ASSOCIATED VISCERAL FAT-RESIDENT GAMMA DELTA T CELLS Marlene E. Starr 1 , 1. University of Kentucky, Lexington, Kentucky, United States
Gamma delta T cells (Tγδ) are a unique group of immune cells that perform both adaptive and innate functions. We recently identified a population of Tγδ cells which show an age-dependent expansion in the visceral fat of both mice and humans. However, little is known regarding the role of these cells in the fat. The purpose of this study was to begin delineating their role by: (1) comparing the gene expression profile of visceral fat-resident Tγδ to conventional T cells (Tconv) and to circulating Tγδ, and (2) identifying agedependent changes in gene expression within the visceral fatresident Tγδ population. Tγδ and Tconv were magnetically purified from blood and visceral fat of young and aged mice. Using NanoString technology, we found that overall transcriptomes of Tγδ in fat and blood were strikingly different. Transcriptomes of Tγδ and Tconv within the fat were more similar, but distinct with the former having high representation of pathways related to inflammation, cytokine and chemokine signaling, and macrophage function and the latter having high representation of pathways related to T-and B-cell function and TNF superfamily. Within the Tγδ population we identified significant (>1.8-fold change, p<0.01) age-associated differences in expression for 8 upregulated genes (C6, Cxcl13, Prg2, Il5ra, Ctla4, Marco, Ccl8, Il10) and 10 downregulated genes (Col4a1,Xcl1,Col1a1,Cfd,Col3a1,Lbp,Thbs1,Klrd1,Il6st,Ccl17). These genes will guide further research aimed at understanding the role of these cells and how their ageassociated changes contribute to chronic inflammation, an underlying component of multiple age-related diseases.

FLAVIN-CONTAINING MONOOXYGENASES (FMOS): LONGEVITY-PROMOTING ENZYMES OR ATHEROSCLEROSIS RISK FACTOR?
Ryan J. Rossner, 1 and Matt Kaeberlein 1 , 1. University of Washington, Seattle, Washington, United States Since their discovery in 1970, flavin-containing monooxygenases (FMOs) have been studied as Phase 1 xenobiotic metabolizing enzymes that act on sulfur-and nitrogen-containing small molecules. In 2015, we demonstrated that C. elegans (worm) fmo-2 was not only necessary for hypoxic response and dietary restriction-mediated lifespan extension, but was also sufficient to extend lifespan when overexpressed. Consistenet with a conserved role for FMOs as longevity-promoting enzymes, mouse hepatic Fmo3 transcript is highly upregulated by numerous major lifespan extending interventions. A contrasting series of reports, however, have described mammalian Fmo3-mediated production of trimethylamine N-oxide (TMAO) as a risk factor for atherosclerosis and other major diseases. My thesis research aims to define the regulation and function of worm fmo-2 using genetic and biochemical approaches. My data thus far support the hypothesis that fmo-2 acts on sulfur amino acid pathway intermediates to promote longevity and healthspan.