About

Bérénice Benayoun, PhD, is an Associate Professor of Gerontology and Biological Sciences at the USC Leonard Davis School of Gerontology. She holds secondary appointments in the Molecular and Computational Biology Department of the USC Dornsife College of Letters, Arts and Sciences, the Biochemistry and Molecular Medicine Department in the Keck School of Medicine of USC, and the Department of Pharmacology and Pharmaceutical Sciences at the USC Mann School of Pharmacy and Pharmaceutical Sciences. She joined the USC faculty in 2017. Her research focuses on epigenome and transcriptome remodeling with aging in vertebrates, exploring how these changes interact with overlooked cues such as biological sex, and their roles in the aging process. Her lab is also a pioneer in developing a naturally short-lived vertebrate model for aging research, the African turquoise killifish (Nothobranchius furzeri). Dr. Benayoun received her undergraduate and graduate degrees at the École Normale Supérieure de Paris and Université Paris Diderot-Paris 7 in France. Her PhD work centered on a transcription factor whose mutations lead to a human syndrome associated with premature menopause. During her postdoctoral training, she identified a new chromatin signature of cell identity and transcriptional consistency, which is partially remodeled during aging, raising important questions about cellular identity stability throughout life. She has been recognized with numerous awards, including the 2020 Pew Biomedical Scholar, the 2021 Nathan Shock New Investigator Award, and the 2024 Vincent Cristofalo Rising Star in Aging Research Award. She is also an associate editor of Geroscience and serves on editorial boards of several scientific journals. Dr. Benayoun has received awards for her mentorship and early career achievements, reflecting her contributions to aging research and her role in advancing the field.

Research topics

• Biology
• Genetics
• Immunology
• Endocrinology
• Cell biology
• Evolutionary biology
• Bioinformatics

Selected publications

• eLife Assessment: An altered cell-specific subcellular distribution of translesion synthesis DNA polymerase kappa (POLK) in aging neurons

  2026-02-19

  peer-reviewOpen access1st authorCorresponding
  PublisherDOI

• The interplay of epigenetic remodelling and transposon-mediated genomic instability in ageing and longevity

  Open Biology · 2026-01-28 · 2 citations

  articleOpen accessSenior author

  Ageing and age-related diseases are the result of complex biological processes that progressively cause deterioration of cellular and tissue function. Among the key hallmarks of ageing are epigenetic alterations and genomic instability, both of which are closely interconnected and significantly contribute to the ageing process. The epigenome, encompassing both DNA and histone modifications, regulates gene expression and maintains genomic integrity throughout life. With age, these regulatory systems become dysregulated, leading to genome-wide changes in chromatin structure, histone modifications and the reactivation of transposable elements (TEs). TEs, typically silenced in heterochromatic regions, become active in aged cells, contributing to genomic instability, mutagenesis, inflammation and metabolic disruption. Despite their significant implications, the role of TEs in the ageing process remains underexplored, and the interplay between epigenomic remodelling and TE activity remains poorly understood. In this review, we explore the molecular mechanisms underlying epigenetic alterations and TE reactivation during ageing, the impact of these changes on genomic stability and the potential therapeutic interventions targeting this interplay. By deciphering the role of epigenetic modifications and TE derepression in the ageing process, we aim to highlight novel avenues for anti-ageing and pro-longevity strategies.

  PublisherOA PDFDOI

• eLife Assessment: Male-biased Cyp17a2 orchestrates antiviral sexual dimorphism in fish via STING stabilization and viral protein degradation

  2026-02-18

  peer-reviewOpen access1st authorCorresponding

  Sex differences can influence physiological responses to exercise, stress or immune responses. For example, males are often more susceptible to viral infections due to hormonal and chromosomal influences. While primary sex determination in mammals is strictly linked to chromosomes, other animals, such as fish, can have a very fluid sex determination, with some fish species lacking sex chromosomes completely. This diversity provides a unique system to study how sexual dimorphism affects immune responses, independent of classical sex-linked pathways. Long-Feng et al. used a fish model with alternative sex determination to test whether non-sex-chromosome genes can affect immune differences between males and females, without the influence of sex chromosomes or hormones. Using genetic and biochemical methods, the researchers demonstrated that male zebrafish are more resistant than females to virus, despite the absence of sex chromosomes. They identified an enzyme called Cyp17a2 to be responsible for this difference, which was present in high amounts in males. This enzyme is usually involved in steroid hormone production, but in species such as zebrafish, it regulates stress hormone production. The experiments revealed that Cyp17a2 boosts antiviral defense in males in two ways. First, it strengthens the fish’s immune signaling by stabilizing a protein known as STING. It does this by adding ubiquitin, a chemical tag that helps the protein to work properly. Second, it directly suppresses viral replication by promoting the breakdown of a viral protein. Moreover, male fish genetically engineered to lack this protein showed reduced immune responses. Overall, these findings suggest that Cyp17a2 is an immune regulator that connects male-specific traits to antiviral defenses. By studying a vertebrate model with alternative sex determination, Long-Feng et al. challenged the mammal-centric view of immune sexual dimorphism that centers on sex chromosomes and hormones and provided new insight into how sex-specific immunity may have evolved. The results prompt reconsideration of the unique mechanisms underlying sex-based immune differences in fish. They may also inform the development of sex-specific strategies to improve disease resistance in economically important fish. Future work should assess the evolutionary conservation of this pathway across vertebrates and explore whether targeting the Cyp17a2 and STING could offer new approaches to antiviral therapy, although clinical applications remain speculative.

  PublisherDOI

• A multi-omic atlas in the African turquoise killifish reveals increased glucocorticoid signaling as a hallmark of brain aging

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-10 · 1 citations

  articleOpen accessSenior authorCorresponding

  Aging is the leading risk factor for cognitive impairment and neurodegeneration, yet molecular changes that unfold in the brain over time, and how they drive this vulnerability, remain unclear. The naturally short-lived African turquoise killifish (Nothobranchius furzeri) offers a powerful model to understand brain aging on an accelerated timescale and test the impact of potential interventions. Here, we present a multi-omic atlas of brain aging of female and male African turquoise killifish from 2 independent genetic strains of different captive lifespans, encompassing single-nuclei RNA-seq, single nuclei ATAC-seq, and bulk ATAC-seq to capture transcriptional and regulatory changes. Interestingly, our atlas indicates that aging leads to a significant expansion of microglia numbers, regardless of sex or strain, which we independently validate using in-situ hybridization. In addition, we identify robust and conserved gene regulation changes, that are consistent with activation of glucocorticoid signalling as a hallmark (and potential driver) of vertebrate brain aging. Furthermore, pharmacological inhibition of glucocorticoid receptor activity starting at middle-age led to significant rescue of key molecular and cellular aging phenotypes. Thus, our study provides a powerful resource and framework to leverage the African turquoise killifish and rapidly uncover actionable pathways driving brain aging.

  PublisherDOI

• Past, present and future perspectives on the science of aging

  Nature Aging · 2026-01-21 · 3 citations

  articleOpen access
  PublisherOA PDFDOI

• Induction of ferroptotic and amyloidogenic signatures linked to Alzheimer’s disease by chemically distinct air pollutants

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-07 · 1 citations

  articleOpen access

  ABSTRACT Air pollution (AirP) exposure is associated with increased Alzheimer’s disease (AD) risk, yet AirP is chemically heterogeneous, complicating identification of shared pathogenic drivers. We examined acute cortical responses to two metal-rich AirP sources, diesel exhaust particles (DEP) and World Trade Center (WTC) dust, and compared them to woodsmoke (WS), a particulate exposure with low metal content. DEP and WTC elicited highly convergent transcriptional responses, sharing over 1200 differentially expressed genes linked to inflammation, ferroptosis, neuronal remodeling, and amyloid processing. These changes were accompanied by impaired antioxidant activity and increased lipid peroxidation within lipid rafts, a membrane microdomain critical for amyloid processing, resulting in increased Aβ generation. In contrast, WS produced a distinct transcriptional signature and failed to induce ferroptotic priming or lipid peroxidation, consistent with its low metal composition. Together, these findings implicate metals as a shared driver linking diverse AirP exposures to amyloidogenic vulnerability and elevated AD risk. Graphical Abstract Acute AirP exposure converges on ferroptotic priming, amyloidogenic processing, and white-matter vulnerability. Acute exposure to metal-rich AirP, such as DEP or WTC introduces redox-active metals and particulate matter that promote lipid peroxidation, amyloidogenesis, and altered transcriptional regulation in the brain. AirP exposure engages xenobiotic metabolism pathways (AhR/ARNT), activates iron and heme handling through ferritinophagy (NCOA4) and heme oxygenase activity (HMOX1), and blunts lipid peroxide detoxification systems, including glutathione peroxidase 4 (GPx4), ferroptosis suppressor protein 1 (FSP1), and glutathione (GSH) synthesis. These changes promote ferroptotic priming and lipid raft oxidation, facilitating amyloid precursor protein (APP) processing by secretases (ADAM10, BACE1, γ-secretase) and increasing amyloid-β (Aβ) generation. In parallel, transcriptional and cell-state remodeling involving neuronal and oligodendrocyte responses contribute to selective white-matter vulnerability, particularly within the corpus callosum. Together, these pathways provide a mechanistic framework linking acute AirP exposure to convergent oxidative, amyloidogenic, and microstructural changes relevant to Alzheimer’s disease pathology.

  PublisherDOI

• Estropausal gut microbiota transplant improves measures of ovarian function in adult mice

  Nature Aging · 2026-03-03 · 2 citations

  articleOpen accessSenior author

  The decline in ovarian function with age affects fertility and is associated with increased risk of age-related diseases, including osteoporosis and dementia. Notably, earlier menopause is linked to shorter lifespan, yet the molecular mechanisms underlying ovarian aging remain poorly understood. Recent evidence suggests the gut microbiota may influence ovarian health. Here we show that ovarian aging is associated with distinct gut microbial profiles in female mice and that the gut microbiome can directly influence ovarian health. Using fecal microbiota transplantation from young or estropausal female mice, we demonstrate that heterochronic microbiota transfer remodels the ovarian transcriptome, reduces inflammation-related gene expression and induces transcriptional features consistent with ovarian rejuvenation. These molecular changes are accompanied by enhanced ovarian health and increased fertility. Integrating metagenomics-based causal mediation analyses with serum untargeted metabolomics, we identify candidate microbial species and metabolites that may contribute to the observed effects. Our findings reveal a direct link between the gut microbiota and ovarian health. To investigate the link between the gut microbiome and ovarian health, here the authors transplant gut microbiota from estropausal female mice to young adult female mice. Microbial transplantation improves ovarian hormone profiles, follicle metrics and fertility-related outcomes, highlighting a causal role for the aging gut microbiome in regulating ovarian function.

  PublisherOA PDFDOI

• eLife Assessment: Male-Biased Cyp17a2 Orchestrates Antiviral Sexual Dimorphism in Fish via STING Stabilization and Viral Protein Degradation

  2026-01-02

  peer-reviewOpen access1st authorCorresponding

  Differences in immunity between males and females in living organisms are generally thought to be due to sex hormones and sex chromosomes, and it is often assumed that males have a weaker immune response. Here we report that in fish, males exhibit stronger antiviral immune responses, the male-biased gene cyp17a2 as a critical mediator of this enhanced response. First, we observed that male zebrafish exhibit enhanced antiviral resistance compared to females, and notably, zebrafish lack sex chromosomes. Through transcriptomic screening, we found that cyp17a2 was specifically highly expressed in male fish. Cyp17a2 knockout males were equivalent to wild-type males in terms of sex organs and androgen secretion, but the ability to upregulate IFN as well as antiviral resistance was greatly reduced. Then, Cyp17a2 is identified as a positive IFN regulator which located at endoplasmic reticulum, and specifically interacts with and enhances STING mediated antiviral responses. Mechanistically, Cyp17a2 stabiles STING expression by recruiting the E3 ubiquitin ligase bloodthirsty-related gene family member 32 (btr32), which facilitates K33-linked polyubiquitination. The capacity of IFN induction of Cyp17a2 was abolished when STING is knockdown. Meanwhile, Cyp17a2 also attenuates viral infection directly to strengthen the antiviral capacity as an antiviral protein, Cyp17a2 degrades the spring viremia of carp virus (SVCV) P protein by utilizing USP8 to reduce its K33-linked polyubiquitination. These findings reveal a sex-based regulatory mechanism in teleost antiviral immunity, broadening our understanding of sexual dimorphism in immune responses beyond the conventional roles of sex chromosomes and hormones.

  PublisherDOI

• Single-nuclei RNA-sequencing uncovers sexually divergent exercise signatures partially mimicked by TFEB overexpression in mouse skeletal muscle

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-26

  articleOpen access

  Exercise induces extensive, cell-type-specific transcriptional remodeling in skeletal muscle to support metabolic flexibility and adaptation. However, the regulatory mechanisms underlying these transcriptional programs, and the extent to which they differ between sexes, remain poorly defined. We previously reported that lifelong, muscle-specific overexpression of human Transcription Factor E-B (cTFEB;HSACre transgenic mice) recapitulates many adaptive features of endurance training in both sexes, leading to profound geroprotective effects during aging even in the absence of exercise. Here, we profile transcriptional adaptations to voluntary wheel running (VWR) and TFEB-overexpression at single-nucleus resolution in young male and female mouse tibialis anterior muscle. This represents, to our knowledge, the first integrated analysis of exercise and TFEB signaling using sex as a biological variable. Using robust bioinformatic and single-nuclei RNA-sequencing approaches, we profiled six muscle-resident cell populations and uncover previously unrecognized, sex-dependent signaling nodes governing exercise-associated metabolic plasticity. TFEB activation and endurance training by VWR elicit strongly correlated transcriptional programs enriched for lipid metabolism, mitochondrial remodeling, and immune modulation, establishing TFEB-overexpression as a partial exercise mimetic. In general, female muscle exhibited enhanced extracellular matrix and lipid-associated responses to endurance training and TFEB overexpression, whereas males preferentially engaged in angiogenic and oxidative networks, revealing distinct sex-specific, sex-dimorphic, or sex-agnostic regulatory routes to metabolic flexibility. Integration with independent multi-omics datasets from endurance-trained rats (MoTrPAC) confirms the conservation of TFEB-exercise transcriptional convergence in skeletal muscle across species and potentially muscle types. Together, these findings define TFEB as a regulator of exercise transcriptional programs and reveal sex-specific molecular frameworks that drive metabolic adaptation in skeletal muscle. Furthermore, the resulting sex-resolved, single-nucleus transcriptional atlas provides a unique resource for the field, enabling comparative, mechanistic, and hypothesis-driven exploration of exercise-responsive skeletal muscle regulatory networks across sexes.

  PublisherOA PDFDOI

• A dual role for cGAS in shaping cellular and organismal responses to genomic instability

  Genes & Development · 2026-04-14

  preprintOpen access

  Mutations in DNA damage repair (DDR) genes lead to genomic instability, driving a range of degenerative syndromes. In addition to promoting mutation accumulation, unrepaired DNA damage can leak into the cytosol and activate innate immune-sensing pathways, particularly the cGAS–STING axis. However, the extent to which cGAS causally contributes to organismal pathology in DDR syndromes in vivo remains unresolved. Here, we genetically model ataxia telangiectasia (A-T) and Bloom syndrome in the short-lived turquoise killifish ( Nothobranchius furzeri ) and demonstrate that genetic disruption of cgas in the A-T model partially ameliorates germline failure, hepatic senescence, and cerebellar neuroinflammation. Unexpectedly, cgas loss also reversed cellular hallmarks of genome instability, including reduced micronuclei, improved telomere integrity, and restored H3K9me3-marked heterochromatin landscape, consistent with STING-independent nuclear functions of cGAS that influence DNA repair and chromatin. Together, these data identify cGAS as a context-dependent amplifier of DDR pathology acting through canonical inflammatory signaling and noncanonical nuclear mechanisms that shape genome stability. Accordingly, our findings support pharmacological cGAS inhibition as a potential strategy for DDR syndromes in settings of chronic DNA damage while highlighting that cgas loss in an otherwise naive background exacerbates pathology and genomic instability, underscoring its essential role in normal physiology.

  PublisherDOI

Recent grants

• Regulation of transcriptional consistency by broad H3K4me3 domains in young cells and during aging

  NIH · $717k · 2015–2021

• Transposable elements as drivers of normal and accelerated aging in Vertebrates

  NIH · $464k · 2019–2022

• Deciphering hormonal regulation of neutrophil biology

  NIH · $2.1M · 2022–2027

• NIH Grant K99AG049934

  NIH · $191k · 2017

Frequent coauthors

• Reiner A. Veitia

  Institut Jacques Monod

  373 shared

• Aurélie Dipietromaria

  Evolution des Régulations Endocriniennes

  188 shared

• Sandrine Caburet

  Institut Jacques Monod

  142 shared

• Frank Batista

  University of Debrecen

  127 shared

• David L’Hôte

  Université Paris Cité

  115 shared

• Anne‐Laure Todeschini

  Institut Jacques Monod

  82 shared

• Adrien Georges

  Inserm

  82 shared

• Marc Fellous

  Bayer (United States)

  74 shared

Labs

• Benayoun LaboratoryPI

Education

• PhD, Paris 7

  University of Paris

  2011

Awards & honors

• 2020 Pew Biomedical Scholar
• 2021 Nathan Shock New Investigator Award from the Gerontolog…
• Rising Star in Reproductive Biology by the Society for Repro…
• 2024 Vincent Cristofalo Rising Star in Aging Research Award…
• 2019 Rosalind Franklin Young Investigator Award in Mammalian…