About

Irina Conboy is a Professor of Bioengineering and is part of the DE Faculty at the Center for Computational Biology at UC Berkeley. She is an associated faculty member with a focus on research areas related to computational biology, biophysics, systems biology, and health. Her role involves contributing to the academic and research environment at the center, and she is connected with graduate students such as Colin Skinner. Her contact email is iconboy@berkeley.edu, and she is involved in the broader activities of the center, including seminars, workshops, and research initiatives.

Research topics

• Immunology
• Psychology
• Medicine
• Biology
• Neuroscience
• Internal medicine
• Cell biology
• Chemistry
• Endocrinology

Selected publications

• Human microphysiological systems of aging recreate the in vivo process expediting evaluation of anti-geronic strategies

  Nature Biomedical Engineering · 2026-03-25 · 1 citations

  articleOpen access

  The search for biological mechanisms of human aging is stalled by a lack of suitable models, and it remains unknown whether and to what degree rejuvenation reported in rodents translates to people. Here we report a human induced pluripotent stem cell-derived microphysiological system modelling the white adipose tissue-liver axis in the presence of heterochronic human serum to study aging and rejuvenation in humans. We reveal changes in functional and molecular hallmarks of aging and rejuvenation. We also investigate unknown biomarkers and mechanisms of plasticity in human tissue aging and potential rejuvenation strategies. The microphysiological chip recapitulates, in 4 days, aging-associated hallmarks that occur after decades of aging in people, including gerontic shifts in gene expression and oxidative DNA damage. We uncover unknown signalling networks in human aging, knock-on effects of aging in fat on liver, sexual polymorphisms of aging and tissue memory of age, and develop a custom machine learning model for biological age. Combining heterochronic human serum with the microphysiological system allows for rapidly establishing human tissue aging, discovering clinically relevant mechanisms and biomarkers, and testing of anti-geronic approaches.

  PublisherDOI

• Plasma Dilution After Myocardial Ischemia–Reperfusion Injury Promotes Cardiac Repair, Heart Performance, and Recovery of Motor Function and Endurance in Old Mice

  Aging Cell · 2026-04-30

  articleOpen accessSenior author

  Myocardial infarction (MI) is the leading cause of cardiovascular-related deaths worldwide, with risk increasing sharply with age. Fibrosis and inflammation occur soon after a pathological event and reflect perturbation of tissue repair that accompanies aging in general. Yet not old, but young animals are typically used for studying MI, emphasizing the unmet need for more relevant preclinical models. We previously determined that plasma dilution, also termed neutral blood exchange (NBE) (replacing ~50% of plasma with saline containing 5% albumin) broadly promotes tissue repair and maintenance, reduces fibrosis and inflammation in old mice, and improves the health of humoral and cellular compartments of blood in old people. Here, we developed a novel preclinical model via combining two complex surgeries in aged mice: jugular vein cannulation followed by plasma dilution with open heart cardiac ischemia-reperfusion (I/R). Using this approach, we found that a single dilution of old plasma that was performed 24 h after I/R significantly and broadly improved the recovery at molecular, cellular, tissue, and functional levels in aged mice. Candidate molecular pathways (JAK/STAT and TGF-β) and target proteins associated with these beneficial effects have been suggested by the bioinformatics on comparative proteomics between sham, I/R, and I/R plus NBE groups. While future studies are needed to establish the detailed processes and safety profiles of plasma dilution as a treatment of MI, this work provides important translational and mechanistic insights into recovery from cardiac injury in aged patients.

  PublisherDOI

• Sex-specific longitudinal reversal of aging in old frail mice

  Aging · 2025-08-21 · 3 citations

  articleOpen accessSenior author

  Important studies report acute rejuvenation of mammalian cells and tissues by blood heterochronicity, old plasma dilution, defined factors, and partial reprogramming. And extension of rodent lifespan via single-prong methods was tried in recent years. Here, we examined whether simultaneous calibration of pathways that change with aging in opposite directions would be more effective in increasing healthspan and lifespan. Moreover, we started with the challenging age group - frail 25-months-old mice that are equivalent to ~75-year-old people. We used an Alk5 inhibitor (A5i) of the age-elevated, pro-fibrotic transforming growth factor-beta (TGF-β) pathway that regulates inflammatory factors, including IL-11, and oxytocin (OT) that is diminished with age and controls tissue homeostasis via G-protein-coupled receptor and ERK signaling. Treatment of old frail male mice with OT+A5i resulted in a remarkable 73% life extension from that time, and a 14% increase in the overall median lifespan. Further, these animals had significantly increased healthspan, with improved physical performance, endurance, short term memory, and resilience to mortality. Intriguingly, these benefits manifested only in the male and not in the female mice, yet OT+A5i had positive effects on fertility of middle-aged female mice. Mechanistically, the bio-orthogonal metabolic proteomics on the blood serum demonstrated that the acute, 7-day, treatment of the old mice with OT+A5i youthfully restored systemic signaling determinants and reduced protein noise in old mice of both sexes. However, after 4 months of OT+A5i, only old male, but not female, mice remained responsive, showing the youthful normalization of systemic proteome. These findings establish the significant health-span extension capacity of OT+A5i and emphasize the differences in aging and in response to longevity therapeutics between the sexes.

  PublisherOA PDFDOI

• Propagation of senescent phenotypes by extracellular HMGB1 is dependent on its redox state

  Metabolism · 2025-04-06 · 12 citations

  article
  PublisherDOI

• In Old Mice, Exercise Induces Inflammation and Fibrosis Unless Alk5‐Inhibitor and Oxytocin Are Used

  Journal of Cellular Physiology · 2025-06-01 · 1 citations

  articleOpen accessSenior authorCorresponding

  Exercise and diet are the best-known methods for attenuating aging-related health decline. However, exercise in older age has diminished gains of strength and agility, and a danger of unrepaired muscle damage. Improving the understanding of age-related differences in response to exercise, our results demonstrate that in old mice, downhill treadmill (eccentric) exercise causes increased influx of CD45+ cells (inflammation) and fibrotic index (fibrosis) in the heart and skeletal muscles. To explain these changes, we identified newly synthesized proteins through bio-orthogonal noncanonical amino acid tagging (BONCAT) and established that exercise exacerbated age-associated protein patterns through a dysregulated transforming growth factor (TGF)-β, Ras/MAPK/PI3Akt, and JAK/STAT pathways. Testing causality, we found that an inhibitor of TGF-β (Alk5 inhibitor, A5i) in combination with the age-diminished peptide oxytocin, previously shown to rejuvenate muscle and brain in sedentary animals, allowed aged mice to exercise without pathologies of skeletal and heart muscles and youthfully restored their de novo proteomes.

  PublisherOA PDFDOI

• Correction for: Sex-specific longitudinal reversal of aging in old frail mice

  Aging · 2025-11-30

  articleOpen accessSenior author

  Aging | doi:10.18632/aging.206345. Cameron Kato, Jessica Zheng, Cindy Quang, Sophia Siopack, Joana Cruz, Zachery R. Robinson, Nicole Fong, Zhixin A. Zhang, Patrick Young, Michael J. Conboy, Irina M. Conboy

  PublisherOA PDFDOI

• Misalignment of age clocks

  GeroScience · 2025-06-25 · 2 citations

  articleOpen accessSenior author

  Biological aging is a complex non-linear process, with markedly distinct starting and end points, yet the biomarkers of its progression remain elusive. A key assumption of most machine learning (ML) approaches for age clocks is that predictive biomedical features can be identified via mathematical transformations of data to favor a linear transition from start to end, even if they erase any natural biological pattern. It is given that expected correlations, e.g., time lived (age) and time left to live (mortality), would persist in such mathematically optimized models, biologically meaningful or not. Here, we further clarify the workings of the clocks, explain the trade-off between mathematical optimization and biological interpretability, and discuss a hallmark of aging, inflammaging, that age clocks struggle to detect. We expand on the negative consequences of incoherence in linear models where some DNA methylation (DNAm) features increase with aging and disease, while others correspondingly decrease, yet positive weights are assigned to both. We quantify the misalignment between major DNAm clocks and actual changes in DNAm, providing an interactive visualization of these errors for each model. We demonstrate that major conventional age clocks are both incoherent and skewed toward leukocyte fractions and that rectifying incoherence makes the model balanced and not skewed toward neutrophils and better detects inflammaging. We briefly outline non-linear ML age clocks and the advantages of identifying a natural trajectory of aging directly from the primary data.

  PublisherOA PDFDOI

• Plasmapheresis as a Potential Generalizable Therapy for Myocardial Infarction

  Rejuvenation Research · 2025-06-04

  review

  Myocardial infarction (MI) remains the leading cause of mortality and morbidity worldwide. It is caused by a thrombotic occlusion of coronary vessel/s that leads to cardiomyocyte death. As a response, inflammatory and fibrotic responses are initiated to replace the necrotic tissue and remodel the heart. However, in most cases, these responses are excessively activated, which accentuates the injury and causes adverse cardiac remodeling, often leading to heart failure. This is highly attributed to the dysregulated repair mechanism brought by reduced regenerative capacity of the adult heart, chronic inflammation, and other patient factors, such as comorbidities, diet, and lifestyle. Because of the negative consequences of excessive inflammation and fibrosis in post-MI responses, inhibiting factors associated with these processes are one of the major approaches in MI management. Several therapies have been developed to broadly and/or selectively inhibit inflammation- and fibrosis-associated proteins over the past decades and have shown promise in addressing post-MI complications. However, challenges ( e.g. , off-targets, problems with drug delivery, dosage, route, and cost) and efficacy of these interventions in the clinical setting remain. Hence, alternative approaches to optimally alleviate these post-MI processes are still much needed. In this review, we discuss the possible use of plasmapheresis, a technique that involves extracorporeal replacement of blood plasma, as a treatment for MI. We provide an overview of the inflammatory and fibrotic responses after MI and focus on how plasmapheresis can be an approach to target these pathways.

  PublisherDOI

• Continuing the Legacy: Understanding and Reducing Tissue Aging to Prevent Many Currently Incurable Diseases

  Rejuvenation Research · 2025-03-10

  editorial1st authorCorresponding
  PublisherDOI

• Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments

  GeroScience · 2025-05-23 · 15 citations

  reviewOpen access

  Aging is a complex biological process that detrimentally affects the brain and cerebrovascular system, contributing to the pathogenesis of age-related diseases like vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD). While cell-autonomous mechanisms that occur within cells, independent of external signals from neighboring cells or systemic factors, account for some aspects of aging, they cannot explain the entire aging process. Non-autonomous, paracrine and endocrine, pathways also play a crucial role in orchestrating brain and vascular aging. The systemic milieu modulates aging through pro-geronic and anti-geronic circulating factors that mediate age-related decline or confer rejuvenative effects. This review explores the impact of systemic factors on cerebrovascular and brain aging, with a particular focus on findings from heterochronic parabiosis, blood exchange, and plasma transfer experiments. We discuss how these factors influence fundamental cellular and molecular processes of aging and impact cerebrovascular endothelial function, neurovascular coupling mechanisms, blood-brain barrier integrity, neuroinflammation, capillary density, and amyloid pathologies, with significant consequences for cognitive function. Additionally, we address the translational potential and challenges of modifying the systemic milieu to promote brain health and prevent age-related cognitive impairment.

  PublisherDOI

Recent grants

• New Generation Blood Exchange Devices for Enhancing Tissue Regeneration and Health

  NIH · $1.6M · 2018–2023

• NIH Grant R56AG048316

  NIH · $156k · 2016

• Defined pharmacology for multi-tissue rejuvenation acting through youthful normalization of p16

  NIH · $381k · 2018–2020

• Treatment of Duchenne Muscular Dystrophy with Cas9 Protein Complexed to Gold Nanoparticles

  NIH · $1.4M · 2017–2022

• NIH Grant K01AG025652

  NIH · $378k · 2009

Frequent coauthors

• Michael J. Conboy

  University of California, Berkeley

  102 shared

• Thomas A. Rando

  VA Palo Alto Health Care System

  37 shared

• Chao Liu

  32 shared

• Melod Mehdipour

  University of California, San Francisco

  25 shared

• Kiana Aran

  25 shared

• Cameron Kato

  University of California, Berkeley

  18 shared

• Colin M. Skinner

  University of California, Berkeley

  16 shared

• Jessy Etienne

  QB3

  16 shared

Labs

• Center for Computational BiologyPI