Therapeutic Immune Reprogramming by Rapamycin Attenuates Plaque Inflammation and Lymphoid Immune Responses in Aged Atherosclerotic Mice

de Mol J, de Korte DH, Depuydt MAC, Smit V, Kleijn MNAB, van Santbrink PJ, Binder CJ, Porsch F, Schaftenaar FH, Foks AC · 2026 · Aging Cell · Atlas ID JIN2026C

What this study shows

In aged atherosclerotic mice, rapamycin (mTORC1 inhibition) reduced plaque macrophage content and total T cell numbers, shifted CD8 T cells from effector to central-memory phenotype, enriched aortic regulatory T cells (higher Foxp3/Tgfb1), reduced Tfh cells, germinal-center B cells, plasma cells and autoantibody levels, diminished age-associated B cells, and lowered senescence-enrichment scores in aortic leukocytes -- consistent with rapamycin acting as an immune-rejuvenation therapeutic that mitigates age-related atherogenic inflammation.

Abstract

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Aging is a major risk factor for atherosclerosis and is accompanied by profound changes in the immune system, including effector T cell expansion, senescent cell accumulation, and increased pro-inflammatory signaling. Rapamycin, a promising rejuvenation therapeutic that inhibits mTORC1 and modulates immune aging, was investigated for its potential to attenuate pro-atherogenic immune responses in aged atherosclerotic mice. 80- to 90-week-old male Ldlr-/- mice with established atherosclerotic lesions were treated intraperitoneally with rapamycin or control triweekly for 8 weeks.

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At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Aged (80-90 wk) male Ldlr-/- mice with established atherosclerosis; rapamycin i.p. triweekly x 8 weeks vs. control); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Aged (80-90 wk) male Ldlr-/- mice with established atherosclerosis; rapamycin i.p. triweekly x 8 weeks vs. control
Journal	Aging Cell
Year	2026
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1111/acel.70730 · PMID 42775680

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Rapamycin, intraperitoneal, three times weekly for 8 weeks
Target	mTORC1 in immune cells (T cell, B cell and macrophage compartments)
Model	Mouse (aged 80-90 week male Ldlr-/-, established atherosclerosis)
Effect	Rapamycin reduced plaque macrophages and effector T cells, enriched regulatory T cells, lowered germinal-centre B cell and antibody responses, and reduced senescence scores in aortic leukocytes.

In the Atlas

Open questions that cite this study

Cited as supporting evidence for the open question Is there a low-dose mTOR schedule whose immune effects come out favourable, compartment by compartment?.

Cite this paper

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de Mol, J., de Korte, D. H., Depuydt, M. A. C., Smit, V., Kleijn MNAB, van Santbrink, P. J., Binder, C. J., Porsch, F., Schaftenaar, F. H., & Foks, A. C. (2026). Therapeutic Immune Reprogramming by Rapamycin Attenuates Plaque Inflammation and Lymphoid Immune Responses in Aged Atherosclerotic Mice. Aging Cell. https://doi.org/10.1111/acel.70730

@article{JIN2026C,
  author       = {de Mol, J. and de Korte, D. H. and Depuydt, M. A. C. and Smit, V. and Kleijn MNAB and van Santbrink, P. J. and Binder, C. J. and Porsch, F. and Schaftenaar, F. H. and Foks, A. C.},
  title        = {{Therapeutic Immune Reprogramming by Rapamycin Attenuates Plaque Inflammation and Lymphoid Immune Responses in Aged Atherosclerotic Mice}},
  journal      = {Aging Cell},
  year         = {2026},
  doi          = {10.1111/acel.70730},
  note         = {PMID: 42775680},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record JIN2026C) [Data set]. https://mtor-atlas.org/study/JIN2026C/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_JIN2026C,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record JIN2026C},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/JIN2026C/},
  doi          = {10.5281/zenodo.22059963}
}

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