MITOCHONDRIAL SYSTEM BIOLOGY AS A WINDOW INTO DISEASES OF AGING

Abstract We identified multiple open-reading-frames (ORFs) within the mitochondrial genome. These ORFs encode putative peptides that we call Mitochondrial-Derived-Peptides (MDPs) which represent a sub-class of a growing group of novel micro-peptides (from both mtDNA and nuclear chromosomes) that serve as signals related to cell and organismal protection and energy expenditure. We described multiple peptides including humanin, SHLPs, and MOTS-c. Exploring mtDNA methylation patterns as well as mito-transcriptomics demonstrated changes in specific ORFs/MDPs in certain diseases. We developed a modified GWAS bioinformatic technique (MiWAS) that identifies SNPs within MDPs that associate with diseases of aging. MOTS-c, and MENTSH, novel anti-obesity/diabetes MDPs, harbors mutation in Asians and Native-Americans, associated with diabetes risk. Thus, MDPs are expressed in an ethno-specific fashion and may contribute to health disparities in a manner related to relevant mitochondrial DNA SNPs. In summary, MDPs are a new class of mitochondrial-hormones that have diagnostic and therapeutic potential in human disease.


MITOCHONDRIAL SYSTEM BIOLOGY AS A WINDOW INTO DISEASES OF AGING Pinchas Cohen 1 , 1. Leonard Davis School of Gerontology, Los Angeles, California, United States
We identified multiple open-reading-frames (ORFs) within the mitochondrial genome. These ORFs encode putative peptides that we call Mitochondrial-Derived-Peptides (MDPs) which represent a sub-class of a growing group of novel micropeptides (from both mtDNA and nuclear chromosomes) that serve as signals related to cell and organismal protection and energy expenditure. We described multiple peptides including humanin, SHLPs, and MOTS-c. Exploring mtDNA methylation patterns as well as mito-transcriptomics demonstrated changes in specific ORFs/MDPs in certain diseases. We developed a modified GWAS bioinformatic technique (MiWAS) that identifies SNPs within MDPs that associate with diseases of aging. MOTS-c, and MENTSH, novel anti-obesity/diabetes MDPs, harbors mutation in Asians and Native-Americans, associated with diabetes risk. Thus, MDPs are expressed in an ethno-specific fashion and may contribute to health disparities in a manner related to relevant mitochondrial DNA SNPs. In summary, MDPs are a new class of mitochondrial-hormones that have diagnostic and therapeutic potential in human disease.

BIOMARKERS OF SENESCENT CELL BURDEN
Nathan LeBrasseur 1 , 1. Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota, United States Senescent cells drive aging. Preclinical studies suggest that targeted elimination of senescent cells offers a unique therapeutic approach to counter numerous chronic diseases and geriatric syndromes. To foster the translation of basic science discoveries to clinical application, we have sought to identify circulating biomarkers that reflect systemic senescent cell burden. We first analyzed the secretome of multiple senescent human cell-types and developed a candidate panel of proteins that could be reliably measured in human blood. Multiple proteins demonstrated significant associations with chronological age in a community-based cohort of adults aged 20-to-90 years. Impressively, in two distinct surgical cohorts (severe aortic stenosis and ovarian cancer), candidate protein concentrations were associated with biological age indices, including frailty and adverse outcomes. Our data suggest senescence biomarkers may have utility for clinical practice as indicators of risk, and for clinical research as surrogate endpoints in trials of interventions targeting senescent cells.
Pay-for-performance programs to incentivize quality are on the rise nationally (Werner, Konetzka, & Polsky, 2013& Arling, Job, & Cooke, 2009). Kansas initiated a Medicaid P4P program to incentivize person-centered care (PCC) beginning in 2012 called PEAK 2.0. This program created an operationalized definition of PCC through stakeholder collaboration and research outcomes (Harris, Poulsen, & Vlangas, 2006). Homes enrolled in the program undergo both self-evaluation and objective external evaluation based on the operationalized definition. These key features inherent in the PEAK 2.0 program make up has aided homes to implement PCC as well as, the ability to research homes that have implemented PCC in a new a different way than ever before. Outcomes related to person-centered care in nursing homes have been difficult to ascertain. Much of the extant literature has suffered from differing definitions of what it means to be person-centered, variation in the levels of implementation of person-centered care that an organization has achieved, and small sample sizes. The PEAK program provides a unique opportunity to control for these variables across a large sample of nursing homes throughout the state of Kansas. This presentation will discuss the methodological advantages of evaluating the PEAK program and the findings from an evaluation of resident satisfaction in nursing homes at varying levels of implementation of person-centeredness. Research opportunities from our organizational partnerships allow us to pursue answers to questions about PCC outcomes that have largely been out of reach for the field. Our program evaluation research agenda includes groundbreaking, short-term clinical outcomes from older Kansans living in nursing facilities implementing increasingly levels of PCC, including a 49% lower prevalence of depression for residents in strong PCC adopting homes (Hermer et al., 2017;Hermer et al., 2018). Yet there have been several challenges to achieving these goals that are atypical to the common academic research process. This presentation will further highlight the clinical outcomes association with PEAK 2.0, our continued research partnership with the state, and highlight some of the unique opportunities and challenges large-scale research with a state organization presents. The goal of PCC is to enhance quality and bring meaning to the lived experience in long-term care. This requires attention to patterns of life, and the creation of residential experiences within the environment. Ten case studies of homes participating in a pay-for-performance PCC program in the Midwest reveals how environmental affordances may be critical in the implementation and sustainability of PCC. Data collected through an in-depth environmental assessment revealed multiple strategies and attributes related to organizational, operational, and environmental practices. This presentation will demonstrate a diagrammatic and empirical comparison of the environments of those early in the process and those who have fully implemented and sustained PCC practices. Specific features will be highlighted and patterns discussed.

PARTNERSHIPS THAT WORK: AN ACADEMIC AND STATE COLLABORATION IN KANSAS
Gayle Doll, 1 Migette Kaup, 1 and Laci Cornelison 1 , 1.

Kansas State University, Manhattan, Kansas, United States
Academic partnership with state government may be a researcher's dream or a tremendous burden. This presentation demonstrates the perspectives of university personnel as well as government leaders when contracts and grants are issued for the provision of research and services. Opportunities and barriers for researchers will be discussed. Long-distance caregiving (LDC) is a growing phenomenon and common experience for caregivers of frail older adults. In fact, 11% of family caregivers in the US live more than two hours distance from the care recipient (CR). Unfortunately, there is a paucity of research on unique experiences of LDCs and the impact of LDC on the mental health of LDCs. This symposium presents findings from the NIA funded Fordham Long-Distance Caregiving Study (R21AG050018) analyzing data of 304 long-distance caregivers (LDCs). The overall study goal was to better understand how LDCs deal with the structural constraint of distance, and to examine LDC consequences and resources. First, Horowitz presents the study background, characteristics of the sample, and provides a description of the unique experiences of LDCs. Next, Cimarolli concentrates on the Sociocultural Stress Process Model applied to LDC. Her study tested the impact of LDC on mental health and investigated resources (e.g., coping skills) which could mediate the association between caregiving stressors and mental health outcomes. The third paper (Falzarano) presents data related to satisfaction with formal service providers for four subgroups of LDCs based on CR residence and dementia status. Finally, Jimenez focuses on the characteristics of LDCs' network of other informal caregivers