ArticleNature cancer2025
Age-associated nicotinamide adenine dinucleotide decline drives CAR-T cell failure.
Article in Nature cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed.
- Changes in ultraviolet a radiation-induced thymidine dimers and erythema after oral nicotinamide or polypodium leucotomos extract in healthy volunteers: a randomized intraindividual trial.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2026Trial
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- The immunology behind inflammaging-causes, sources, and mechanisms.The Journal of allergy and clinical immunology · 2026Review
- Adipose FGF21 signalling mediates the anti-senescence effects of protein restriction.The Journal of physiology · 2026Article
- Cytotoxic CD4Nature aging · 2026Article
- Nicotinamide Metabolism Constrains Memory CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nicotinamide riboside enhances adoptive T cell therapy by promoting memory differentiation and metabolic fitness.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Oral LNAD+ rapidly elevates whole blood intracellular NAD and metabolic flux without elevating plasma NAD: evidence from a randomized controlled trial.GeroScience · 2026Article
- Implications of Rho GTPase signaling in cancer immunotherapy.Biochemical Society transactions · 2026Review
- Nicotinic Acid Restriction Enhances the Therapeutic Benefit of NAMPT Inhibition in Small-Cell Lung Cancer Models.Cancer science · 2026Article
- Mitochondrial Dysfunction in Circulating Blood Cells and Biological Aging: A Review of Mechanisms and Evidence.Biomolecules · 2026Review
- Characteristics and utilization of the three BCMA-targeted therapies in multiple myeloma.International journal of hematology · 2026Review
- Regulation of T Cell Senescence in Health and Diseases.Immune network · 2026Review
- Metabolic Crosstalk Between Host and Tumor as a Circuit of Resilience in Cancer Therapy.Cells · 2026Review
- Skeletal Muscle Redox Signaling in Health and Disease: From Molecular Mechanisms to Therapeutic Exercise Strategies.Antioxidants (Basel, Switzerland) · 2026Review
- Natural Small Molecules Targeting Oxidative Stress and Redox Homeostasis in Aging: Mechanisms and Therapeutic Potential.Antioxidants (Basel, Switzerland) · 2026Review
- Article
- Determinants of Chimeric Antigen Receptor (CAR) T Cell Success: In Vitro and In Vivo Preclinical Assessment.Cancers · 2026Review
- Redox index and capacity analysis (RICA) reveals NAD biology changes in T cell responses in vitro and ex vivo.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Memory programming and new manufacturing paradigms in CAR-T cell therapy.Cancer gene therapy · 2026Review
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Chimeric antigen receptor (CAR) T cell therapy is one of the most promising cancer treatments. However, different hurdles are limiting its application and efficacy. In this context, how aging influences CAR-T cell outcomes is largely unknown. Here we show that CAR-T cells generated from aged female mice present a mitochondrial dysfunction derived from nicotinamide adenine dinucleotide (NAD) depletion that leads to poor stem-like properties and limited functionality in vivo. Moreover, human data analysis revealed that both age and NAD metabolism determine the responsiveness to CAR-T cell therapy. Targeting NAD pathways, we were able to recover the mitochondrial fitness and functionality of CAR-T cells derived from older adults. Altogether, our study demonstrates that aging is a limiting factor to successful CAR-T cell responses. Repairing metabolic and functional obstacles derived from age, such as NAD decline, is a promising strategy to improve current and future CAR-T cell therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.