In 80- to 90-week-old Ldlr-/- mice with established atherosclerotic lesions, eight weeks of rapamycin reduced plaque macrophage content, lowered T cell numbers in vascular and lymphoid tissue, and shifted the remaining population toward central memory and regulatory phenotypes. Antigen-driven humoral responses also fell, including T follicular helper cells, germinal center B cells, plasma cells, and oxidation-specific epitope antibodies, alongside markedly reduced senescence signatures in aortic leukocytes. The work positions mTORC1 inhibition as an immune-directed rather than purely lipid-directed approach to age-related vascular disease.
Key Points
- Rapamycin cut plaque macrophage content by roughly 23 percent
- Effector T cells shifted toward central memory and regulatory phenotypes
- Aortic leukocyte senescence scores and age-associated B cells declined
Longevity Analysis
Atherosclerosis in older arteries is sustained as much by an aging immune compartment as by circulating lipids, and this work separates those contributions by targeting the immune side alone. Suppressing antigen-driven lymphoid activity while enriching regulatory populations addresses the low-grade inflammatory interference that accumulates with age and drives arterial wall damage — an intervention applied to established disease, not prevention. The reduction in senescent immune signatures within the vessel wall points to a measurable readout that could eventually guide dosing and timing rather than leaving mTOR inhibition as an empirical practice.
Original published by Wiley Aging Cell, by Jill de Mol, Daphne H. de Korte, Marie A. C. Depuydt, Virginia Smit, Mireia N. A. Bernabé Kleijn, Peter J. van Santbrink, Christoph J. Binder, Florentina Porsch, Frank H. Schaftenaar, Amanda C. Foks .