About

Joseph A. Baur, PhD, is a Professor of Physiology at the Perelman School of Medicine at the University of Pennsylvania. His research centers on the molecular mechanisms of aging and metabolism, with a particular focus on NAD metabolism and mTOR signaling pathways. His work aims to elucidate how these pathways influence healthspan and lifespan, especially through interventions such as caloric restriction, genetic modifications, and small molecule treatments. Dr. Baur's laboratory investigates the transport and synthesis of NAD within mammalian cells and mitochondria, identifying key transporters like SLC25A51 and exploring how NAD levels impact mitochondrial function and aging-related diseases. Additionally, his research examines the effects of rapamycin and mTOR signaling on longevity, metabolic health, and side effects such as hyperlipidemia, with the goal of developing targeted therapies to delay aging and age-associated diseases. His collaborative projects also explore the impact of sleep disruption on endocrine function and neurodegenerative conditions like Alzheimer’s disease. Dr. Baur is a member of several institutes, including the Institute for Diabetes, Obesity & Metabolism, the Institute on Aging, and the Center of Excellence in Environmental Toxicology, and he directs the Mouse Phenotyping, Physiology, and Metabolism Core at the Diabetes Research Center.

Research topics

• Biology
• Biochemistry
• Chemistry
• Cell biology
• Medicine
• Internal medicine
• Endocrinology
• Immunology
• Neuroscience
• Bioinformatics
• Oncology
• Cancer research
• Computational biology
• Pharmacology
• Intensive care medicine
• Ecology
• Psychology

Selected publications

• Code and notebooks for "Competitive catabolism in systemic mammalian metabolic homeostasis"

  Zenodo (CERN European Organization for Nuclear Research) · 2026-04-02

  otherOpen access

  This repository accompanies the paper "Competitive catabolism in systemic mammalian metabolic homeostasis" and contains the code and models used in the study, including the mechanistic multi‑nutrient model and the detailed mitochondrial model, together with simulation functions, Jupyter notebooks, and analysis scripts to reproduce figures and experiments.

  PublisherDOI

• Clock Regulation of Metabolites Reveals Coupling between Transcription and Metabolism

  UNC Libraries · 2026-01-14

  articleOpen access
  PublisherDOI

• In vivo imaging of glutamate uncovers the neuroprotective effects of nicotinamide riboside on excitotoxicity in an Alzheimer’s mouse model

  Alzheimer s Research & Therapy · 2026-01-30

  articleOpen access

  Nicotinamide adenine dinucleotide (NAD+) precursors, such as nicotinamide riboside (NR), have gained interest as potential therapeutics for alleviating Alzheimer’s disease (AD) pathology. Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) can provide insights into the effects of NR on AD by virtue of its sensitivity to monitoring the metabolic status of tissue in vivo. This study used glutamate-weighted CEST (GluCEST) MRI to monitor glutamate-associated metabolic changes following NR treatment in the 5xFAD mouse model of AD. Drinking water was supplemented with NR or provided as is to animals over the course of expected disease progression prior to imaging experiments. Following imaging, an immunohistochemical assay to monitor the expression of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (Iba1) was performed to assess the extent of neuroinflammatory glial responses. A two-way ANCOVA with interaction was performed for statistical analysis of both CEST and IHC data. Results from GluCEST revealed significantly higher glutamate levels in the hippocampal dentate gyrus of AD mice compared to WT, with a significant reduction following treatment. GFAP staining mirrored this trend, implicating reactive astrogliosis as a mechanism for elevated glutamate. Similar patterns were observed in the cerebral peduncles, a white matter bundle, in which GFAP and Iba1 supported GluCEST findings and suggested neuroinflammation in axonal tracts. Our findings are in concordance with studies reporting elevated glutamate associated with reactive gliosis and morphological changes disrupting glutamate imbalance. Interestingly, NR restores glutamate homeostasis and alleviates neuroinflammatory processes, thus rescuing tissue from excitotoxic insults. Overall, this study demonstrates the potential of NR to mitigate glutamate-driven excitotoxicity in AD pathology, and highlights GluCEST as a sensitive in vivo, clinically translatable biomarker for neuroinflammation and excitotoxicity.

  PublisherDOI

• Safety and efficacy of individualised exercise and NAD+ precursor supplementation in patients with Friedreich's ataxia in the USA: a single-centre, 2 × 2 factorial, randomised controlled trial

  The Lancet Neurology · 2026-04-17 · 1 citations

  articleOpen access

  BACKGROUND: precursor supplementation with nicotinamide riboside, which have each shown benefits in animal and early clinical studies, on cardiopulmonary fitness in individuals with Friedreich's ataxia. METHODS: . Stage 1 analysis tested the difference between each active treatment versus the control group, and stage 2 analysis (if combination therapy was effective) tested the difference between combination treatment and exercise alone; family-wise type 1 error was maintained <0·05. Analyses were by intention-to-treat. Adverse events were recorded systematically. This trial is registered with ClinicalTrials.gov (NCT04192136) and is complete. FINDINGS: =0·0299) for nicotinamide riboside and exercise in combination. Combination therapy was not statistically different from exercise alone (difference -0·05 ([95% CI -0·10 to 0·21]; p=0·49). Adverse events were all mild or moderate, and included gastrointestinal symptoms, falls, upper respiratory infections, and skin rashes. At least one moderate adverse event of interest in these categories was reported by seven (41%) participants in the control group; six (35%) in the nicotinamide riboside and no exercise group; three (19%) in the placebo and exercise group; and four (25%) in the nicotinamide plus exercise group. INTERPRETATION: The combination of nicotinamide riboside plus exercise for 12 weeks was safe and increased cardiopulmonary fitness in children and adults with Friedreich's ataxia. Longer studies are needed to establish whether adding nicotinamide riboside to exercise could be considered as part of a long-term, comprehensive treatment approach. FUNDING: US National Institutes of Health and Friedreich's Ataxia Research Alliance.

  PublisherDOI

• Code and notebooks for "Competitive catabolism in systemic mammalian metabolic homeostasis"

  Zenodo (CERN European Organization for Nuclear Research) · 2026-04-02

  otherOpen access

  This repository accompanies the paper "Competitive catabolism in systemic mammalian metabolic homeostasis" and contains the code and models used in the study, including the mechanistic multi‑nutrient model and the detailed mitochondrial model, together with simulation functions, Jupyter notebooks, and analysis scripts to reproduce figures and experiments.

  PublisherDOI

• ERα activates NAMPT/IL-33 signaling to enhance beige thermogenesis and metabolic fitness

  Science Advances · 2026-01-07

  articleOpen access

  Beige adipocytes are inducible thermogenic fat cells that emerge within white adipose tissue (WAT) in response to thermogenic stimuli and confer metabolic benefits. However, obesity impairs the generation of beige adipocytes, and the underlying mechanisms remain poorly understood. Here, we show that obesity leads to a loss of adipose progenitor cells (APCs) in WAT, accompanied by reduced estrogen (E2) levels and nicotinamide phosphoribosyltransferase (NAMPT) expression. Supplementation with E2 or nicotinamide mononucleotide (NMN), an NAMPT-derived nicotinamide adenine dinucleotide (NAD + ) precursor, restores beige adipogenesis in diet-induced obese mice. Mechanistically, estrogen receptor α (ERα) in APCs is required for beige fat formation by promoting Nampt transcription. We further demonstrate that NAMPT is both necessary and sufficient to drive APC proliferation and differentiation, with interleukin-33 (IL-33) acting downstream to mediate these effects. These findings uncover a critical ERα/NAMPT/IL-33 axis that preserves progenitor function and thermogenic capacity, offering a potential therapeutic strategy to combat obesity-induced beige fat failure and associated metabolic dysfunction.

  PublisherDOI

• NAD-dependent redox control enables endothelial quiescence and vascular stabilization during angiogenesis

  Cell Metabolism · 2026-04-01

  articleOpen access
  PublisherOA PDFDOI

• Lactate homeostasis is maintained through regulation of glycolysis and lipolysis

  Cell Metabolism · 2025-01-30 · 51 citations

  articleOpen access
  PublisherOA PDFDOI

• A consensus guide to preclinical indirect calorimetry experiments

  Nature Metabolism · 2025-09-24 · 14 citations

  reviewOpen access
  PublisherOA PDFDOI

• Abstract 4338158: The metabolome is preserved in failing mouse hearts but shifts under additional stress

  Circulation · 2025-11-03

  articleSenior author

  The healthy heart is omnivorous as it readily utilizes fatty acids, glucose, lactate, pyruvate, ketone bodies, and amino acids. This adaptation enables the heart to metabolize alternative fuels when the preferred fatty acids for maximal ATP production cannot be utilized due to decreased cardiac efficiency. It is well established that the failing human heart ultimately becomes metabolically insufficient as it gradually shifts to fuels such as ketone bodies and fails to generate enough ATP to compensate for the energy deficit. While mouse HF models are being utilized to elucidate underlying pathomechanisms and explore metabolic therapy targets, the metabolome of the failing mouse heart is not well characterized. Thus, using stable isotope-labeled metabolites, we sought to characterize the global metabolome and fuel utilization in failing mice myocardia. We hypothesize the metabolome and fuel utilization of the failing mice heart will change substantially like failing human hearts. To assess the metabolic phenotype of the failing mice heart, we induced HFrEF in mice with TAC/MI surgeries, followed by echocardiography after 4 weeks to assess systolic functions and morphometrics. Next, cocktails of isotope-labeled metabolites (glucose, lactate, β-OHB, glutamine, and valine) were infused intravenously for 2 hr while arterial blood was collected at different time points. Alternatively, isoproterenol (90 ng/kg/min) was added to the cocktail to mimic ambulatory heart rates while metabolites were being infused. Intriguingly, the metabolome of the TAC/MI with reduced LVEF compared to the Sham showed only 7.2% of myocardial metabolite levels altered; principal component analysis (PCA) showed no overt change in the metabolome. Similarly, isotope tracing data showed no differences in metabolite enrichment and fuel utilization in the myocardia. However, TAC/MI drastically altered the response to additional stress with isoproterenol, with 34.9% of metabolites changed in myocardial metabolomics between TAC/MI and Sham. Also, PCA showed a significantly diverging metabolic profiling between the failing and normal hearts from TAC/MI and Sham mice, respectively – representing similar observations in failing human hearts. We show for the first time that metabolome is preserved in failing mouse hearts but shifts under stress, thus warranting further investigation into the dynamics of the metabolic profile of the failing heart for insights into developing metabolic therapies for HF.

  PublisherDOI

Recent grants

• University of Pennsylvania Diabetes Research Center

  NIH · $17.0M · 1997–2027

• NIH Grant R01AG043483

  NIH · $2.0M · 2020

• Targeting NAD Metabolism to Improve Glucose Homeostasis in Obesity and Aging

  NIH · $6.1M · 2013–2029

• NIH Grant K99AG031182

  NIH · $90k · 2009

• NIH Grant R00AG031182

  NIH · $732k · 2012

Frequent coauthors

• Dudley W. Lamming

  William S. Middleton Memorial Veterans Hospital

  41 shared

• David M. Sabatini

  Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry

  33 shared

• Rafael de Cabo

  National Institute on Aging

  29 shared

• Karthikeyani Chellappa

  29 shared

• David Sinclair

  Harvard University

  29 shared

• James G. Davis

  University of Pennsylvania

  24 shared

• Joshua D. Rabinowitz

  Princeton University

  23 shared

• Zoltán Ungvári

  Semmelweis University

  22 shared

Education

• Other, Chemistry

  Acadia University

  1998

• Ph.D., Integrative Biology

  UT Southwestern Medical Center

  2003

Awards & honors

• Featured in issue highlights
• Fellowship in the Faculty of 1000