Bérénice A Benayoun

Bérénice A Benayoun
University of Southern California | USC · School of Gerontology

PhD in Genetics

About

106
Publications
15,360
Reads
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3,823
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Introduction
Bérénice A Benayoun currently works at the School of Gerontology, University of Southern California. Bérénice does research in Bioinformatics, Genetics and Systems Biology.
Additional affiliations
April 2011 - present
Stanford University
Position
  • PostDoc Position
September 2007 - February 2011
Paris Diderot University
Position
  • PhD Student

Publications

Publications (106)
Article
Full-text available
Widespread sex-dimorphism is observed in the mammalian immune system. Consistently, studies have reported sex differences in the transcriptome of immune cells at the bulk level, including neutrophils. Neutrophils are the most abundant cell type in human blood, and they are key components of the innate immune system as they form a first line of defe...
Article
Rationale: The role of neutrophils and their extracellular vesicles (EVs) in the pathogenesis of pulmonary arterial hypertension is unclear. Objectives: Relate functional abnormalities in pulmonary arterial hypertension neutrophils and their EVs to mechanisms uncovered by proteomic and transcriptomic profiling. Methods: Production of elastase,...
Article
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. In addition, accumulating evidence indicates that sex horm...
Article
Biological sex is a fundamental source of phenotypic variability across species. Males and females have different nutritional needs and exhibit differences in nutrient digestion and utilization, leading to different health outcomes throughout life. With personalized nutrition gaining popularity in scientific research and clinical practice, it is im...
Article
While investigating sex differences in T cell aging, Mkhikian et al. identified a role for excessive IL-7 signaling and N-glycan branching in age-related T cell dysfunction in women and female mice. These findings point to the increasingly recognized importance of the effects of biological sex on immune aging, and delineate new targetable pathways...
Article
In this study, we investigate the hypothesis that recently identified longevity‐promoting intervention 17α‐estradiol (17αE2) will protect against senescent changes in brain and throughout the body that are associated with APOE4 and heightened AD risk. The most significant genetic factor for late‐onset Alzheimer’s disease (AD) is the apolipoprotein...
Article
Background: The predominant genetic risk factor for late-onset Alzheimer's disease (AD) is the ε4 allele of apolipoprotein E (APOE4). APOE4-related risk of developing AD is modified by sex, with women showing greater risk than men. Regardless of APOE genotype, women exhibit a higher prevalence and lifetime risk of AD. Extensive human and animal mo...
Article
Full-text available
Longevity is often associated with stress resistance, but whether they are causally linked is incompletely understood. Here we investigate chemosensory defective Caenorhabditis elegans mutants that are long-lived and stress resistant. We find that mutants in the intraflagellar transport protein gene osm-3 were significantly protected from tunicamyc...
Article
Full-text available
Neutrophils are the most abundant human white blood cell and constitute a first line of defense in the innate immune response. Neutrophils are short-lived cells and thus the impact of organismal aging on neutrophil biology, especially as a function of biological sex, remains poorly understood. Here, we describe a multi-omic resource of mouse primar...
Preprint
Full-text available
The aggresome is a protein turnover system in which proteins are trafficked along microtubules to the centrosome for degradation. Despite extensive focus on aggresomes in immortalized cell lines, it remains unclear if the aggresome is conserved in all primary cells and all cell-states. Here we examined the aggresome in primary adult mouse dermal fi...
Article
Full-text available
Researchers need in vitro models that mirror the biology of organisms. Primary fibroblasts play essential roles in wound healing and are present in many tissues. They are widely used in studies of cell cycle control, reprogramming, and aging. Though extraction protocols exist, alternatives that maximize use of available resources are useful. Here,...
Article
The aging population is at a higher risk for age-related diseases and infections. This observation could be due to immunosenescence: the decline in immune efficacy of both the innate and the adaptive immune systems. Age-related immune decline also links to the concept of ‘inflamm-aging,’ whereby aging is accompanied by sterile chronic inflammation....
Article
Full-text available
Healthy aging can be promoted by enhanced metabolic fitness and physical capacity. Mitochondria are chief metabolic organelles with strong implications in aging that also coordinate broad physiological functions, in part, using peptides that are encoded within their independent genome. However, mitochondrial-encoded factors that actively regulate a...
Article
An extensive multiomic resource using human monocytes reveals large-scale remodeling of DNA methylation landscapes in healthy aging and accelerated or pathological aging contexts. This work provides an invaluable resource with important implications for the study of age-related changes in immune function.
Article
Full-text available
The existence of human supercentenarians reveals a surprising predictor for exceptional longevity: being female. Not only are 33 out of 34 living supercentenarians women, women are also more resistant to most diseases responsible for age-related morbidity in the US. However, because most molecular aging studies generally opt to use only one sex, se...
Article
Full-text available
Revolutionary advancements of high-throughput sequencing and metagenomic tools have provided new insights to microbiome function, including a bidirectional relationship between the microbiome and host aging. The intestinal tract is the largest surface in the human body that directly interacts with foreign antigens – it is covered with extremely com...
Article
Our understanding of the molecular regulation of aging and age-related diseases is still in its infancy, requiring in-depth characterization of the molecular landscape shaping these complex phenotypes. Emerging classes of molecules with promise as aging modulators include transposable elements, circRNAs and the mitochondrial transcriptome. Analytic...
Chapter
The majority of age-related diseases share common inflammatory mechanisms, a phenomenon which has been described as “inflamm-aging,” and genetic variants in immune and inflammatory genes are significantly associated with exceptional human longevity and/or age-related diseases. Consistently, aging is associated with increased macrophage infiltration...
Article
Full-text available
Although aging is a conserved phenomenon across evolutionary distant species, aspects of the aging process have been found to differ between males and females of the same species. Indeed, observations across mammalian studies have revealed the existence of longevity and health disparities between sexes, including in humans (i.e. with a female or ma...
Article
Full-text available
In multi-cellular organisms, the control of gene expression is key not only for development, but also for adult cellular homeostasis, and deregulation of gene expression correlates with aging. A key layer in the study of gene regulation mechanisms lies at the level of chromatin: cellular chromatin states (i.e. the ‘epigenome’) can tune transcriptio...
Article
Full-text available
The current cohort of human supercentenarians reveals a surprising predictor for achieving such an exceptional longevity: being female. Indeed, out of 34 living supercentenarians, 33 are women. We obtained samples from 4 and 20 months old female and male mice. Our data indicates that cytokine levels are differentially regulated with age in males vs...
Article
Full-text available
“Inflamm-aging” describes a state of chronic low-grade inflammation which occurs with age in the absence of infection. This process is related to many chronic age-related diseases. Aryl hydrocarbon receptor (Ahr), is a transcription factor that is thought to decrease inflammation, and decrease of Ahr with aging only in females was previously observ...
Article
Full-text available
Age-associated chronic inflammation (inflammageing) is a central hallmark of ageing¹, but its influence on specific cells remains largely unknown. Fibroblasts are present in most tissues and contribute to wound healing2,3. They are also the most widely used cell type for reprogramming to induced pluripotent stem (iPS) cells, a process that has impl...
Article
Full-text available
Aging is accompanied by the functional decline of tissues. However, a systematic study of epigenomic and transcriptomic changes across tissues during aging is missing. Here, we generated chromatin maps and transcriptomes from four tissues and one cell type from young, middle-aged, and old mice-yielding 143 high-quality data sets. We focused on chro...
Article
Full-text available
In multi-cellular organisms, the control of gene expression is key not only for development, but also for adult cellular homeostasis, and gene expression has been observed to be deregulated with aging. In this review, we discuss the current knowledge on the transcriptional alterations that have been described to occur with age in metazoans. First,...
Article
The functional decline of tissues is a hallmark of aging. A systematic study of genomic changes during aging has not been done, and may reveal important principles of genetic dysregulation with age. To understand how chromatin may impact tissue function during aging, we focused on chromatin marks linked to cell identity, broad H3K4me3 regions and c...
Article
This symposium will present exciting new model organisms for aging research, and highlight important novel discoveries that they have enabled. These models encompass Rotifers, microscopic, aquatic invertebrates that are easy to culture and transparent, the naked mole rat, an extremely long-lived eusocial rodent, and the African turquoise killifish,...
Poster
Full-text available
Calorie Restriction (CR), or the restriction of caloric intake without malnutrition, may improve health and delay aging across species by targeting cellular nutrient-sensing pathways to improve the metabolic profile. Recent work suggests that CR may act at the epigenetic level by altering DNA methylation and histone modifications. These changes sho...
Poster
Full-text available
Genomic instability is one of the hallmarks of aging; it can be caused by many factors(e.g. mutations, aneuploidy, exposure to mutagens, or activation of endogenous transposable elements [TEs]). TEs are also known as “jumping genes,” since they can transpose from one region in the host genome to another. Eukaryotic genomes consist of 30% - 80% of T...
Preprint
Age-associated chronic inflammation (inflammaging) has emerged as a central hallmark of aging1-3, but its impact on specific cells is still largely unknown. Fibroblasts are present in all tissues and contribute to wound healing4-6. They are also the cell type that is mostly used for induced pluripotent stem cell (iPSC) reprogramming7 - a process th...
Preprint
Full-text available
Aging is accompanied by the functional decline of tissues. However, a systematic study of epigenomic and transcriptomic changes across tissues during aging is missing. Here we generated chromatin maps and transcriptomes from 4 tissues and one cell type from young, middle-age, and old mice, yielding 143 high-quality datasets. We focused specifically...
Data
Differentially expressed genes for H2AFJ over-expression.
Data
TopGO gene ontology analyses for differentially expressed genes.
Data
Differentially expressed genes in senescent versus proliferating cells.
Data
Differentially expressed genes for sh-H2AFJ versus sh-NoTarget.
Data
Differentially expressed genes and FKPM data for RNA-seq of sh2-H2AFJ versus sh-NoTarget in senescent cells.
Article
Full-text available
The senescence of mammalian cells is characterized by a proliferative arrest in response to stress and the expression of an inflammatory phenotype. Here we show that histone H2A.J, a poorly studied H2A variant found only in mammals, accumulates in human fibroblasts in senescence with persistent DNA damage. H2A.J also accumulates in mice with aging...
Article
Full-text available
Reviewers: This article was reviewed by Zoltan Gaspari and Piotr Zielenkiewicz.
Article
Full-text available
Summary Lifespan is a remarkably diverse trait ranging from a few days to several hundred years in nature, but the mechanisms underlying the evolution of lifespan differences remain elusive. Here we de novo assemble a reference genome for the naturally short-lived African turquoise killifish, providing a unique resource for comparative and experime...
Article
Full-text available
Telomerase inactivation causes loss of the male germline in worms, fish, and mice, indicating a conserved dependence on telomere maintenance in this cell lineage. Here, using telomerase reverse transcriptase (Tert) reporter mice, we found that very high telomerase expression is a hallmark of undifferentiated spermatogonia, the mitotic population wh...
Article
Full-text available
AMP-activated protein kinase (AMPK) is a central energy gauge that regulates metabolism and has been increasingly involved in non-metabolic processes and diseases. However, AMPK's direct substrates in non-metabolic contexts are largely unknown. To better understand the AMPK network, we use a chemical genetics screen coupled to a peptide capture app...
Article
Full-text available
Ageing is affected by both genetic and non-genetic factors. Here, we review the chromatin-based epigenetic changes that occur during ageing, the role of chromatin modifiers in modulating lifespan and the importance of epigenetic signatures as biomarkers of ageing. We also discuss how epigenome remodelling by environmental stimuli affects several as...
Article
One of the invariant features of human cancer is unlimited proliferation, a hallmark conferred by telomerase in 90% tumors. Somatic mutations in the telomerase reverse transcriptase (TERT) gene promoter are highly recurrent in human cancers. Telomerase is also critically important in human stem cells, as evidenced by mutations in telomerase, which...
Article
Full-text available
Video abstract: Aging is a complex process that affects multiple organs. Modeling aging and age-related diseases in the lab is challenging because classical vertebrate models have relatively long lifespans. Here, we develop the first platform for rapid exploration of age-dependent traits and diseases in vertebrates, using the naturally short-lived...
Article
Mutations in the retinoblastoma tumor suppressor gene Rb are involved in many forms of human cancer. In this study, we investigated the early consequences of inactivating Rb in the context of cellular reprogramming. We found that Rb inactivation promotes the reprogramming of differentiated cells to a pluripotent state. Unexpectedly, this effect is...
Article
Full-text available
Trimethylation of histone H3 at lysine 4 (H3K4me3) is a chromatin modification known to mark the transcription start sites of active genes. Here, we show that H3K4me3 domains that spread more broadly over genes in a given cell type preferentially mark genes that are essential for the identity and function of that cell type. Using the broadest H3K4m...
Article
Full-text available
How the longevity of individuals of one sex is affected by those of the opposite sex is still largely unclear. In the nematode Caenorhabditis elegans, the presence of males accelerated aging and shortened the life span of individuals of the opposite sex (hermaphrodites), including long-lived or sterile hermaphrodites. The male-induced demise could...
Article
Full-text available
Ovarian granulosa cell tumors (OGCT) are the most frequent kind of sex cord-stromal tumors, and represent ∼2-5% of all ovarian malignancies. OGCTs exist as two entities, juvenile and adult types, with specific clinical and pathological characteristics. The molecular pathogenesis of these tumors has just begun to be unraveled. Indeed, recent studies...
Article
Full-text available
FOXL2 transcription factor is responsible for the Blepharophimosis Ptosis Epicantus inversus Syndrome (BPES), a genetic disease involving craniofacial malformations often associated with ovarian failure. Recently, a somatic FOXL2 mutation (p.C134W) has been reported in >95% of adult-type granulosa cell tumors. Here, we have identified 10 novel FOXL...
Article
Full-text available
Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. No...
Data
Classification of transcription factors in TFe. There are 803 human, mouse, and rat articles in TFe, most of which are organized into groups, families and subfamilies of TFs. The classification scheme utilized in TFe is derived from the work of Fulton et al. [5] in TFCat. There are 8 large groups, which are further subclassified into 34 families. S...
Data
Full-text available
PDF of released article. The PDF version of the human FOXL2 article. Other PDF versions of released TFe articles can be accessed on the TFe website.
Data
Relationship Between Pfam domains and PDB records. A list of Pfam binding domains followed by PDB records in which the domains can be found.
Data
Data of released articles. Additional data related to the released mini review articles to supplement the four-page PDF versions, arranged in alphabetical order by TF name.
Data
Full-text available
The TFe article structure. Articles in TFe are organized into ten tabs labeled 'Summary', 'Structure', 'TFBS', 'Targets', 'Protein', 'Interactions', 'Genetics', 'Expression', 'Ontologies', and 'Papers'. Each tab, with the exception of the Ontologies and Papers tabs, typically begins with a brief overview written by the authors, followed by a mixtur...
Data
Full-text available
Binding models produced in the TFe project. Images of the binding models produced in TFe that are sufficiently characterized to be used in a study.
Data
PDB records depicting protein-DNA binding interface. A list of PDB records that depict a protein-DNA binding interface.
Article
Full-text available
Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. No...
Article
Full-text available
A recent study by Greer et al. in the nematode C. elegans has shown transgenerational epigenetic inheritance of longevity in the descendants of worms deficient for subunits of a complex responsible for histone H3 lysine 4 trimethylation (H3K4me3). In this commentary, we discuss the implications of this epigenetic memory of longevity and the potenti...
Article
Full-text available
Chromatin modifiers regulate lifespan in several organisms, raising the question of whether changes in chromatin states in the parental generation could be incompletely reprogrammed in the next generation and thereby affect the lifespan of descendants. The histone H3 lysine 4 trimethylation (H3K4me3) complex, composed of ASH-2, WDR-5 and the histon...