Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction
Abstract via Crossref
Abstract Senescent cells, which accumulate in organisms over time, contribute to age-related tissue decline. Genetic ablation of senescent cells can ameliorate various age-related pathologies, including metabolic dysfunction and decreased physical fitness. While small-molecule drugs that eliminate senescent cells (‘senolytics’) partially replicate these phenotypes, they require continuous administration. We have developed a senolytic therapy based on chimeric antigen receptor (CAR) T cells targeting the senescence-associated protein urokinase plasminogen activator receptor (uPAR), and we previously showed these can safely eliminate senescent cells in young animals. We now show that uPAR-positive senescent cells accumulate during aging and that they can be safely targeted with senolytic CAR T cells. Treatment with anti-uPAR CAR T cells improves exercise capacity in physiological aging, and it ameliorates metabolic dysfunction (for example, improving glucose tolerance) in aged mice and in mice on a high-fat diet. Importantly, a single administration of these senolytic CAR T cells is sufficient to achieve long-term therapeutic and preventive effects.
Evidence snapshot note
This reference is cited by the validated MVA · BUB1B evidence snapshot (data as of 2026-10-17) as Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction.
- Model in the source
- Naturally aged C57BL/6 mice and high-fat-diet mice.
- Where in the publication
- Figures 3-5 (clearance, safety assessments and metabolic endpoints); Figures 6-7 (persistence/prevention and high-fat diet).
- Cited by evidence records
- MVA-IMMUNE-011
The note describes how the snapshot used the source; it is not a summary of the publication's conclusions.
Identifiers and provenance
- DOI
10.1038/s43587-023-00560-5- PMID
38267706- PMCID
PMC10950785- Metadata from
- Crossref, Europe PMC, OpenAlex, fetched
- License (as declared by the source)
- https://creativecommons.org/licenses/by/4.0
- Open access
- Yes
- Added
- from the MVA evidence snapshot
In the library
- Collections
- MVA Hackathon 2026 — BUB1B
- Tags
- None yet
- Keywords from the source
- cellular senescence, urokinase-type plasminogen activator receptor, uPAR, exercise capacity, glucose tolerance, high-fat diet, single-dose therapy, aging, senolytics