Prophilactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1019240 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26117249.fastq.gz | Fastqsanger.gz | |||
| SRR26117250.fastq.gz | Fastqsanger.gz | |||
| SRR26117251.fastq.gz | Fastqsanger.gz | |||
| SRR26117252.fastq.gz | Fastqsanger.gz | |||
| SRR26117253.fastq.gz | Fastqsanger.gz |
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Project description: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.
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