Integrated Physiology of Aging Core (IPAC)
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The Integrative Physiology of Aging Core (IPAC) of the San Antonio (SA) Nathan Shock Center provides intellectual and technical services to internal and external scientists on the selection, design, and conduct of functional assays in rodents and marmosets at the molecular, tissue/organ, and whole-organism levels. The Core achieves its goals through the following Aims: 1) To assist investigators with the design of experiments and the selection of tests to measure age-associated functional changes. 2) To coordinate Core activities with other SA Shock Center and institutional resources to maximize the impact of each individual project. 3) To carry out integrative (from systemic to molecular) functional assessments and analyze and interpret data. 4) To disseminate knowledge through hands-on training and education of researchers, locally, and throughout the National Shock Center Program, on concepts and tools used in the field. IPAC provides services in (a) metabolism and bioenergetics, (b) neuromuscular and cardiac function, and (c) cognitive and non-cognitive brain functions. Services are also matrixed by level: molecular, tissue/organ, and whole-organism. The Core can perform focused functional phenotyping within one or more domains and levels, or batteries of coordinated functional assessments that include measures from all three domains. During the present funding cycle, the IPAC served 63 investigators (2.8-fold increase from the previous period), many external to UTHSCSA, resulting in 194 publications, leading to 80 funded grant proposals. Examples of discoveries made with support from the IPAC include: the first demonstration of cellular senescence in the etiology of Alzheimer's disease; the identification of the cardiolipin-remodeling enzyme ALCAT1 as a key link between cellular senescence and mitochondrial dysfunction in age-related pathology; the finding that mTOR is involved in the pathogenesis of vascular dementia; the discovery of TMEM127 as a new component of mTOR complex 1 that controls development, growth and metabolism; the elucidation of NFκB as a central modulator of insulin sensitivity and muscle growth throughout the lifespan; characterization of physiologic and hematologic effects of long-term mTOR inhibition with rapamycin in the marmoset; and elucidation of numerous physiologic changes with aging in the marmoset that lay the foundation for interventional studies in this species. The IPAC advances the field by employing emerging animal models of exceptional interest in aging. For example, a unique feature of the Core is the development of the common marmoset as a model of aging to help close the translational gap between rodent and human physiologic studies. Other innovations proposed in this period include (1) measures of cellular and whole body resilience; (2) functional lipidomics to assess the role of lipid metabolism and signaling in aging; and (3) single cell assessments in rodents and marmosets.
