About

Sean Curran, PhD, is a Professor of Gerontology and Molecular and Computational Biology at the USC Leonard Davis School of Gerontology, where he also serves as Vice Dean, Dean of Faculty, and Dean of Research. He is co-director of the USC-Buck Nathan Shock Center of Excellence in the Basic Biology of Aging. His research group focuses on defining molecular, genetic, and environmental factors that impact health parameters such as resistance to environmental and dietary stress, mobility, metabolism, reproductive fitness, and mitochondrial function throughout life. The long-term goal of his work is to generate blueprints that enable individuals to maximize health over their lifespan, informed by genetics to predict ideal diets for a healthy life and identify diets to avoid. Curran developed the first PhD in Geroscience program, which recruited its inaugural class in 2024. His research is funded by the NIH and has received support from various foundations and organizations. He is a Fellow of the Gerontological Society of America and has received numerous awards for his research, including the AFAR Vincent Cristofalo Rising Star in Aging Research Award, the Paul F. Glenn Award, and the Nathan Shock New Investigator Award. Curran's mentoring has been recognized by the Mellon Foundation, and he received the USC Provost’s Mentoring Award in 2019. He earned his PhD from UCLA and completed post-doctoral training at Harvard Medical School and Massachusetts General Hospital.

Research topics

• Biology
• Genetics
• Cell biology
• Biochemistry
• Physiology
• Biotechnology
• Microbiology

Selected publications

• Astaxanthin, meclizine, mitoglitazone, pioglitazone, alpha-ketoglutarate, mifepristone, methotrexate, and atorvastatin-telmisartan do not increase lifespan in UM-HET3 mice

  GeroScience · 2026-03-17

  articleOpen access

  The Interventions Testing Program (ITP) evaluated eleven compounds in genetically heterogeneous UM-HET3 mice to assess their potential to extend lifespan. These interventions included both novel agents and previously tested compounds administered at novel doses or starting ages. Despite prior evidence suggesting lifespan benefits of these proposed interventions in other models or under different conditions, none of the tested compounds significantly increased lifespan in male or female mice. Notably, astaxanthin, mitoglitazone, and meclizine-previously associated with lifespan extension in the ITP-showed no benefit when administered at different doses or starting at later ages. In females, astaxanthin, late-start mitoglitazone, and pioglitazone were associated with significantly reduced lifespan when pooling the data from all three sites. However, site-specific analysis revealed unusually long lifespans in control females at The Jackson Laboratory, prompting reanalysis using data from the other two sites and only showed a negative effect for mitoglitazone and pioglitazone. This study underscores the importance of rigorous, multi-site testing and highlights the challenges of translating promising initial findings into consistent lifespan benefits at other doses or with alternate starting ages. These results suggest that timing and dosage are critical variables in aging intervention studies and reinforce the need for cautious interpretation of single-site or single-cohort findings.

  PublisherOA PDFDOI

• Activated SKN-1 alters the aging trajectories of long-lived <i>Caenorhabditis elegans</i> mutants

  Genetics · 2025-01-28 · 3 citations

  articleOpen accessSenior author

  In the presence of stressful environments, the SKN-1 cytoprotective transcription factor is activated to induce the expression of gene targets that can restore homeostasis. However, chronic activation of SKN-1 results in diminished health and a reduction of lifespan. Here, we demonstrate the necessity of modulating SKN-1 activity to maintain the longevity-promoting effects associated with genetic mutations that impair daf-2/insulin receptor signaling, the eat-2 model of dietary restriction, and glp-1-dependent loss of germ cell proliferation. A hallmark of animals with constitutive SKN-1 activation is the age-dependent loss of somatic lipids, and this phenotype is linked to a general reduction in survival in animals harboring the skn-1gf allele. Surprisingly, daf-2lf; skn-1gf double mutant animals do not redistribute somatic lipids, which suggests the insulin signaling pathway functions downstream of SKN-1 in the maintenance of lipid distribution. As expected, the eat-2lf allele, which independently activates SKN-1, continues to display somatic lipid depletion in older ages with and without the skn-1gf activating mutation. In contrast, the presence of the skn-1gf allele does not lead to somatic lipid redistribution in glp-1lf animals that lack a proliferating germline. Taken together, these studies support a genetic model where SKN-1 activity is an important regulator of lipid mobilization in response to nutrient availability that fuels the developing germline by engaging the daf-2/insulin receptor pathway.

  PublisherOA PDFDOI

• SEROTONIN SIGNALING IN HOST-PATHOGEN RESPONSES

  Innovation in Aging · 2025-12-01

  articleOpen access1st authorCorresponding

  Abstract When an organism encounters a pathogen, the host innate immune system activates to defend against pathogen colonization and toxic xenobiotics produced. C. elegans employ multiple defense systems to ensure survival when exposed to Pseudomonas aeruginosa including activation of the cytoprotective transcription factor SKN-1/NRF2. Although wildtype C. elegans quickly learn to avoid pathogens, here we describe a peculiar behavior in animals with constitutive activation of SKN-1 whereby they choose not to leave the pathogenic environment even when a non-pathogenic and healthspan-promoting food options are available. SKN-1 activation, specifically in neurons and intestinal tissues, orchestrates a unique transcriptional program which leads to defects in serotonin signaling that is required from both neurons and non-neuronal tissues. Serotonin depletion from SKN-1 activation limits pathogen defenses capacity, drives the pathogen-associated apathy behaviors and induces a synthetic sensitivity to selective serotonin reuptake inhibitors. We further define the serotonin receptors required for this behavioral response to Pseudomonas. Taken together, our work reveals interesting insights into how animals perceive environmental pathogens and subsequently alter behavior and cellular programs to promote survival.

  PublisherOA PDFDOI

• Parental age selection in <i>C. elegans</i> influences progeny stress resistance capacity

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-06

  preprintOpen accessSenior authorCorresponding

  ABSTRACT With parental age rising around the globe, an increased understanding of the impact on health and longevity is needed. Here, we report how the continuous selection of the last progeny during the Caenorhabditis elegans reproductive span results in a diminishment of multiple age-related health measures. After more than fifty generations of late selection, progeny displayed diminished resistance to acute oxidative stress, disrupted partitioning of stored lipids, reduced movement capacity, and an overall shortening of lifespan. In contrast, starvation resistance was improved and late selection had negligible effects on developmental timing and total reproductive output that suggests a reduction in lifespan health to preserve reproductive capacity. The phenotypes of late selection are reminiscent of animals with activation of the cytoprotective transcription factor SKN-1 but are unlikely a result of a spontaneous genetic mutation. These findings suggest the existence of a homeostatic mechanism for bookmarking the temporal boundaries of the parental reproductive span that reshapes the way we think about parental age influencing offspring fitness.

  PublisherOA PDFDOI

• Evolutions in Mentoring to Engineer Opportunity

  Innovation in Aging · 2025-12-01

  articleOpen access1st authorCorresponding

  Abstract The Hiram J. Friedsam Award lecture will feature an address by the 2025 award recipient, Sean Curran, PhD, FGSA, Hiram J. Friedsam was the professor, co-founder, and director of the Center for Studies in Aging and dean of the School of Community Service at the University of Northern Texas. Dr. Friedsam was an outstanding teacher, researcher, colleague, and mentor to students, faculty, and administrators, as well as a past president of AGHE. The purpose of this award is to recognize those who emulate Dr. Friedsam’s excellence in mentorship.

  PublisherDOI

• Presidential Symposium: Integrating Geroscience Across Scale

  Innovation in Aging · 2025-12-01

  articleOpen access1st authorCorresponding
  PublisherOA PDFDOI

• WormRACER: Robust Analysis by Computer-Enhanced Recording

  GeroScience · 2025-03-26 · 5 citations

  articleOpen accessSenior author

  The pace of scientific high-throughput screening for age-related phenotypes requires the need for developing streamlined and efficacious methods of measuring and quantifying physiological outcomes and at a scale that enables adequate statistical power to measure the variation in populations. Here, we introduce Worm Robust Analysis by Computer-Enhanced Recording (WormRACER), a computationally efficient computer vision software capable of extracting six different crawling and swimming metrics from many animals simultaneously, including worm area, worm length, crawling speed, swimming speed, dynamic amplitude, and wave initiation rate (thrashing). Additionally, we developed a web-based portal that provides metric averages and metric vs time graphs that allow for simple data analysis and quality assurance. WormRACER will facilitate the rapid and quantitative characterization of movement as a facile measurement of healthspan enabling power for high-throughput screening of genetic, environmental, and pharmacological interventions.

  PublisherOA PDFDOI

• Parental age selection in <i>C. elegans</i> influences progeny stress resistance capacity

  The Journals of Gerontology Series A · 2025-10-30

  articleOpen accessSenior author

  With parental age rising around the globe, an increased understanding of the impact on health and longevity is needed. Here, we report how the continuous selection of the last progeny during the Caenorhabditis elegans reproductive span results in a diminishment of multiple age-related health measures. After more than 50 generations of late selection, progeny displayed diminished resistance to acute oxidative stress, disrupted partitioning of stored lipids, reduced movement capacity, and an overall shortening of lifespan (36.84% reduction). In contrast, starvation resistance was improved and late selection had negligible effects on developmental timing and total reproductive output that suggests a reduction in lifespan health to preserve reproductive capacity. The phenotypes of late selection are reminiscent of animals with activation of the cytoprotective transcription factor SKN-1 that may facilitate transcriptional remodeling following late reproductive selection. These findings suggest the existence of a homeostatic mechanism for bookmarking the temporal boundaries of the parental reproductive span that reshapes the way we think about parental age influencing offspring fitness.

  PublisherOA PDFDOI

• Building an Interdisciplinary Workforce in Geroscience: Aligning Perspectives and Educational Goals

  The Journals of Gerontology Series A · 2025-04-24

  articleOpen access

  The National Institute on Aging-funded Geroscience Education and Training Network held the "Building an Interdisciplinary Workforce in Geroscience: Aligning Perspectives and Educational Goals" preconference workshop at the 2023 Gerontological Society of America's Annual Meeting. Parties involved in geroscience education and interested stakeholders addressed the development of didactic educational materials, training, and career development opportunities to equip learners with the skills to meet the demands of the emerging field of geroscience, from research to clinic and industry. Recent successes were presented, existing opportunities, gaps, and challenges identified and discussed, and solutions and future directions described.

  PublisherOA PDFDOI

• Loss of WDR23 slows the rate of age-related cognitive decline with elevated amyloid burden

  Journal of Alzheimer s Disease · 2025-05-04 · 1 citations

  articleSenior authorCorresponding

  Background WDR23 is a regulator of cellular proteostasis and oxidative stress response processes that are critically involved in the pathogenesis of Alzheimer's disease (AD). Dysregulation of these pathways can contribute to amyloid-β (Aβ) and tau pathologies, ultimately leading to cognitive impairment. Objective We explored the effects of Wdr23 knockout on key AD-related pathologies, including transcriptomic changes, Aβ and tau pathology, and cognitive function in the 3xTg-AD mouse model of early onset familial AD. Methods Transcriptomic analysis of hippocampal tissue was performed to identify Wdr23 -dependent gene expression changes across age groups. Aβ and tau pathology was assessed via immunohistochemistry. Behavioral assays were conducted to determine cognitive function and locomotor activity. Results Transcriptomic data revealed an age-dependent effect of Wdr23 knockout on gene expression, with enrichment of pathways related to cognition and synaptic plasticity, especially middle-age and aged mice. Interestingly, while Wdr23 knockout exacerbated amyloid plaque accumulation in older mice, it did not impact tau pathology. Behaviorally, Wdr23 knockout mice exhibited improved cognitive function and enhanced activity levels compared to wild-type counterparts, suggesting a dissociation between Aβ pathology and cognitive performance. Additionally, we observed age-related changes in NRF2 target gene activation but declined in Wdr23 knockout mice over time. Conclusions Our findings highlight a complex relationship between proteostasis, amyloid pathology, and cognitive outcomes in AD, warranting further investigation into the specific mechanisms by which Wdr23 modulates these processes. This study suggests that targeting proteostasis pathways could offer potential therapeutic benefits, particularly in preserving cognitive function, even in the presence of amyloid pathology.

  PublisherDOI

Recent grants

• NIH Grant K99AG032308

  NIH · $197k · 2011

• NIH Grant R01GM109028

  NIH · $1.8M · 2020

• Genomic Translation Across Species Core

  NIH · $11.2M · 2020–2026

• USC-Buck Geroscience Training in the Biology of Aging

  NIH · $4.5M · 2016–2027

• NIH Grant RF1AG063947

  NIH · $2.9M · 2024

Frequent coauthors

• Alexander A. Soukas

  Harvard University

  16 shared

• Nicole L. Stuhr

  University of Southern California

  16 shared

• Dana A. Lynn

  University of Southern California

  13 shared

• Gary Ruvkun

  Brandeis University

  12 shared

• Chia‐An Yen

  University of Southern California

  11 shared

• Chatrawee Duangjan

  University of Southern California

  10 shared

• Carla M. Koehler

  University of California, Los Angeles

  10 shared

• Lucydalila Cedillo

  Massachusetts General Hospital

  9 shared

Education

• Ph.D., Gerontology

  USC Leonard Davis School of Gerontology

  2026

Awards & honors

• AFAR Vincent Cristofalo Rising Star in Aging Research Award
• Paul F. Glenn Award
• Nathan Shock New Investigator Award (GSA)
• Ewald W. Busse Research Award
• USC Provost’s Mentoring Award (2019)