New Aspects in Metabolism of Aging

Abstract In recent years there has been a renewed emphasis on metabolism as a key contributor to a host of chronic non-communicable conditions: cancer, neurodegeneration, frailty, and functional declines in immune and inflammatory processes. All share a common connection in metabolic dysfunction. Furthermore, aging itself is associated with changes in metabolism, although the underlying drivers for these changes are unknown. Here we introduce speakers working at the cutting edge in metabolism research, and whose studies are of direct relevance to aging. Dr. Chandel will focus on mitochondrial biology, describing recent advances in understanding the mechanisms of the beneficial effects of metformin. Dr. Haigis takes the mitochondrial theme to cancer biology, the area of research that revived metabolic perspectives in biomedical research. Dr. Najt’s talk describes a less well studied organelle, the lipid droplet, and its role in a rapidly expanding area of research on lipid metabolic regulation specifically in the context of aging. Dr. Brown-Borg will present data on nutritional and genetic modulation of metabolism and how pathways converge to influence chromatin and epigenetic regulation of gene expression. Together our speakers explore new concepts in metabolism research that are of particular relevance to aging. This session aligns with the concept of GeroScience, the more we know of aging biology the better we understand diseases and disorders of aging. This session will demonstrate that metabolism, its regulation, and its influence on key processes linked to health and longevity, place it in a central position as we seek to discover targets and interventions to improve human aging.

regression analysis to determine whether sociodemographic characteristics, cause of death, or receipt of family caregiving explained the observed differences in place of death by foreign-born status. Results from fully adjusted multivariate models indicate the foreign-born differences in place of death cannot be explained by socioeconomic, health, or family factors. Our research shows key differences in the end-of-life experience between US-born and foreign-born older adults and highlights the importance of examining end-of-life experiences for this small, but rapidly growing segment of the older U.S. population.

WHERE TO RETIRE? EXPERIENCES OF OLDER AFRICAN IMMIGRANTS IN THE UNITED STATES
Manka Nkimbeng, 1 Alvine Akumbom, 2 Marianne Granbom, 3 Sarah Szanton, 4 Tetyana Shippee, 5 Roland Thorpe, Jr., 6 and Joseph Gaugler, 1 1. University of Minnesota,Minneapolis,Minnesota,United States,2. Johns Hopkins School of Nursing,Baltimore,Maryland,United States,3. Centre of Ageing and Supportive Environments (CASE),Lund University,Skane Lan,Sweden,4. Johns Hopkins University,Baltimore,Maryland,United States,5. University of Minnesota,University of Minnesota,Minnesota,United States,6. Johns Hopkins Bloomberg School of Public Health,baltimore,Maryland,United States The needs and conceptualization of age-friendliness likely vary for immigrant older adults compared to native-born older adults. For example, Hispanic immigrant older adults often return to their home country following the development of ill health. Doubling in size since the 1970's, the aging needs of African immigrants are not fully understood. This qualitative study examined experiences of aging and retirement planning for African immigrant older adults in the United States (U.S.). Specifically, it explored the factors, processes, and ultimate decision of where these older adults planned to retire. We analyzed semi-structured interviews with 15 older African immigrants in the Baltimore-Washington Metropolitan area. Data were analyzed using thematic analyses in NVivo. The majority of participants were women, with a mean age of 64. We identified three overarching themes with ten sub-themes. The themes included: 1) cultural identity: indicating participant's comfort with the U.S. society and culture; 2) decision making: factors that impact participants' choice of retirement location, and 3) decision made: the final choice of where participants would like to retire. Age-friendliness for immigrant older adults in the U.S. is complex and it includes the traditional domains such as physical and sociocultural environment (e.g. housing, transportation, and income). However, immigrant age-friendliness also needs to include wider contextual aspects such as political climate in their country of origin, immigrant status, family responsibilities, and acculturation in the U.S. More research is needed understand and facilitate age-friendly environments for transnational immigrant older adults.

NEW ASPECTS IN METABOLISM OF AGING Chair: Rozalyn Anderson
In recent years there has been a renewed emphasis on metabolism as a key contributor to a host of chronic noncommunicable conditions: cancer, neurodegeneration, frailty, Innovation in Aging, 2021, Vol. 5, No. S1 and functional declines in immune and inflammatory processes. All share a common connection in metabolic dysfunction. Furthermore, aging itself is associated with changes in metabolism, although the underlying drivers for these changes are unknown. Here we introduce speakers working at the cutting edge in metabolism research, and whose studies are of direct relevance to aging. Dr. Chandel will focus on mitochondrial biology, describing recent advances in understanding the mechanisms of the beneficial effects of metformin. Dr. Haigis takes the mitochondrial theme to cancer biology, the area of research that revived metabolic perspectives in biomedical research. Dr. Najt's talk describes a less well studied organelle, the lipid droplet, and its role in a rapidly expanding area of research on lipid metabolic regulation specifically in the context of aging. Dr. Brown-Borg will present data on nutritional and genetic modulation of metabolism and how pathways converge to influence chromatin and epigenetic regulation of gene expression. Together our speakers explore new concepts in metabolism research that are of particular relevance to aging. This session aligns with the concept of GeroScience, the more we know of aging biology the better we understand diseases and disorders of aging. This session will demonstrate that metabolism, its regulation, and its influence on key processes linked to health and longevity, place it in a central position as we seek to discover targets and interventions to improve human aging.

METHIONINE METABOLISM IN AGING REGULATION Holly Brown-Borg, University of North Dakota School of Medicine & Health Sciences, Grand Forks, North Dakota, United States
Aging is the major risk factor for many diseases but the mechanisms are poorly understood. The risk of developing hepatic steatosis increases with age and the health impact of this disease is negative and high. When challenged with high fat diets, long living Ames mice withstand the detrimental metabolic effects that occur in normal mice. We examined transcriptomic and epigenomic profiles of Ames and wild type hepatocytes in the presence or absence of fat to demonstrate that the epigenomic profile drives transcription factor and downstream gene expression resulting in susceptibility or resistance to fatty liver disease. We found that markers of steatosis are related to gene expression in wild type and Ames mice, and dwarf mice retain fewer lipid droplets compared to wild type mice. These studies will provide data to guide our understanding of mechanisms leading to hepatic disease and define factors that provide protection from age-related metabolic disorders.

METFORMIN INHIBITS MITOCHONDRIAL COMPLEX I TO PROMOTE HEALTH Navdeep Chandel, Northwestern University, Illinois, United States
The major function of mitochondria in cellular homeostasis has been the generation of ATP through oxidative phosphorylation. However, we have previously demonstrated that mitochondria can serve as signaling organelles by releasing low levels of reactive oxygen species (ROS) and TCA cycle metabolites that are essential for hypoxic activation of HIF, antigen activation of T cells, cellular differentiation and proliferation of cancer cells. The anti-diabetic drug metformin has been proposed to inhibit mitochondrial complex I. We will present data indicating that metformin inhibits mitochondrial complex I to exert it's biological effects through controlling ROS, ATP, and NAD+.

LIPID DROPLET SIGNALING IN METABOLIC HEALTH AND AGING
Charles Najt, 1 and Douglas Mashek, 2 1. University of Minnesota,2. University of Minnesota,Minneapolis,Minnesota,United States Lipid droplets (LDs) are neutral lipid rich organelles involved in lipid storage, fatty acid trafficking, and signaling. Emerging evidence from our laboratory and others suggests that the specific LD resident proteins couple/uncouple cells and tissues from inflammation and metabolic dysfunction. However, the mechanism by which LD proteins influences these critical pathways remains unknown. We will present data delving into the role of LD proteins Perilipin (PLIN) 2 and 5 in balancing cellular energy metabolism, mitochondrial function, and inflammation. Data will be presented defining novel mechanisms through which PLIN2 orchestrates eicosanoid production as a means to promote inflammation. We will contrast these findings to PLIN5, which uncouples LD accumulation from metabolic dysfunction and inflammation, in part due to its promotion of SIRT1 signaling. Overall, these studies will highlight a crucial role of LD metabolism and signaling in regulating cellular energy homeostatic processes known to be key players in governing healthspan. Health care is important for maintaining optimal physical and mental health. However, due to the COVID-19 pandemic, many older adults have delayed or postponed care. Data from the special midterm release of the 2020 Health and Retirement Study (HRS) were used to examine the relationship between chronic conditions and delayed care, as well as between delayed care and mental health outcomes and preventative care among Americans aged 50+ (N=3,266). Approximately 30% of respondents said yes when asked "Since March 2020, was there any time when you needed medical or dental care, but delayed getting or did not get it at all?" Of those, 55% said their provider cancelled, closed or suggested rescheduling, 28.5% decided it could wait, and 20.8% were afraid to go. Results from OLS and