Assistant Professor, USC, Leonard Davis School of Gerontology
Lab Website
Genomic regulation of Vertebrate aging
Friday, October, 11
12 PM
RRI 101
Abstract: The overarching goal of the Benayoun laboratory is to understand how aging influences the epigenome, and in return, how modulation of the epigenome can influence the aging process. We want to understand how this interaction is modulated in response to environmental stimuli and in the context of specific endogenous factors, specifically sex, invertebrate organisms. Aging is accompanied by striking changes in chromatin and gene expression across cell types and species. Yet, how chromatin landscapes change with age and regulate transcription, and how epigenomic changes in turn influence aging in response to external or internal cues, is largely unknown.
Such knowledge will be critical to counteract the functional decline associated with physiological aging, and its exacerbation in age-related disease. A critical aspect of our research is the use of multiple vertebrate model organisms. The short lifespan of non-vertebrate model systems (e.g. yeasts, worms, and flies) makes their use in experimental aging research very attractive, and they have been widely used to explore genetic and environmental underpinnings of aging. However, as a result of this experimental pragmatism, our understanding of mechanisms that regulate vertebrate aging, including the role of vertebrate-specific genes, organs, and tissues (e.g. bones and blood), and physiological processes (e.g. adaptive immunity), significantly lags behind.
These considerations led us to spearhead the de novo sequencing, assembly, and annotation of the African turquoise killifish genome, the shortest-lived vertebrate that can be bred in captivity. Despite this compressed lifespan, the African turquoise killifish display all key age-related phenotypes, including age-related cognitive decline. Our work has transformed the use of this organism as a vertebrate model, and we now are able to leverage this powerful new model organism in conjunction to established traditional models to rapidly identify novel pathways regulating aging and longevity in vertebrates.
Our main cell model of study are key components of the innate immune system and the inflammatory response: macrophages, which accomplish key tasks such as phagocytosis, antigen presentation, and cytokine production. Consistently, aging is associated with increased macrophage infiltration into tissues. Macrophages have two main origins: tissue-resident macrophages differentiate from specific embryonic progenitors, whereas monocyte-derived macrophages differentiate from bone-marrow progenitors throughout life.
Resident macrophage populations exist across tissues. Because of their key role in inflammation and damage repair, macrophages are a key cell type in age-related inflammatory diseases. Specific ongoing research directions in the Benayoun lab focus on (i) identifying transcriptional and epigenomic changes with age and upon interventions which extend vertebrate longevity, (ii) dissecting transcriptional regulation changes throughout life, as well as underlying molecular mechanisms for these changes, and (iii) understanding the regulation of aspects of aging by sex, an important, yet very much understudied, factor in aging and longevity.
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