Colchicine targets ALDH2 in radiation-induced macrophage senescence and atherosclerosis
In cell and animal experiments plus patient macrophage samples, low-dose colchicine directly activated ALDH2 and reduced radiation-induced macrophage senescence and atherosclerosis; the abstract reports these as findings, not proven human benefits. [1]
Automatic summary · not editorially reviewed
The key findings
In a cell-free assay, colchicine directly activated ALDH2 dose-dependently with a half-maximal effective concentration of 1–5 nM. [1]
In a partial carotid ligation model, colchicine attenuated radiation-induced atherosclerosis and macrophage senescence-associated stemness. [1]
Macrophages from patients after radiation therapy showed reduced ALDH2 with increased mitochondrial reactive oxygen species, lipid peroxidation and senescence. [1]
The source at a glance
- Study type / format
- Preclinical laboratory and animal study with patient macrophage samples (abstract)
- Population / context
- Bone marrow–derived macrophages, human monocyte-derived macrophages from thoracic malignancy patients, and a mouse partial carotid ligation model.
- Summary based on
- Study abstract
- Publication status
- Preprint · peer-review status not confirmed
- Original publication
- May 30, 2026
Colchicine and ALDH2 in irradiated macrophages
The abstract asks how low-dose colchicine protects blood vessels and whether it limits radiation-associated vascular injury. Bone marrow–derived macrophages were pretreated with low-dose colchicine and exposed to 2 Gy ionizing radiation; effects were studied with RNA sequencing, immunoblotting and molecular docking. In a cell-free assay, colchicine directly activated aldehyde dehydrogenase 2 (ALDH2) in a dose-dependent manner, with a half-maximal effective concentration of 1–5 nM, identifying ALDH2 as a direct molecular target.
Supporting source [1]
ALDH2-dependent protection in cells and mice
After irradiation, colchicine restored ALDH2, reduced mitochondrial reactive oxygen species–dependent p90 ribosomal S6 kinase activation and lipid peroxidation, preserved TET2 and DNMT3A expression, and rescued impaired efferocytosis while preventing depletion of nicotinamide adenine dinucleotide (NAD⁺) and adenosine triphosphate (ATP). These effects were ALDH2-dependent: they were lost when ALDH2 was inhibited or depleted and mimicked by pharmacological ALDH2 activation. In vivo, in a partial carotid ligation model using spatial proteomics, colchicine attenuated radiation-induced atherosclerosis and macrophage senescence-associated stemness.
Supporting source [1]
Patient macrophages after radiotherapy and abstract limits
Macrophages derived from human monocytes of patients with thoracic malignancy were analyzed before and after radiation therapy. After radiotherapy, these macrophages showed reduced ALDH2 together with increased mitochondrial reactive oxygen species, lipid peroxidation and senescence. The authors conclude that ALDH2 is a previously unrecognized colchicine target linking mitochondrial redox control to suppression of radiation-induced macrophage senescence and atherosclerosis, and that this may contribute to low-dose colchicine's efficacy in cardiovascular disease. Only the abstract was reviewed; the full text was not reviewed, so design details, sample sizes and follow-up are not reported here.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. Cell-free, cell-culture, mouse-model and patient-macrophage findings are reported; no human clinical outcome or lifespan benefit is established, and associations are not causes.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Abe J, Samanthapudi VS, Chen W, Lee J, Tra NT, Mejia GF, Hoang O, Rivera LA, Chu KY, Osawa M, Kim JH, Li S, Ko KA, Reddy AK, López Moreno SF, Lenz SA, Ostos Mendoza K, Sanchez EG, Deswal A, Herrmann J, Schadler KL, Yvan-Charvet L, Manisty C, Ameri P, Yusuf SW, Pathania R, Burks JK, Palaskas NL, Nead KT, Hidebrandt M, Fuller CD, Koutrompakis E, Krishnan S, Lin SH, Wang G, Le N, Kotla S. · europepmc.org · May 30, 2026