What this means
Atherosclerosis is an age-related immune-metabolic disease in which lipid retention, endothelial dysfunction, innate immune activation, and vascular remodeling interact over decades. In older adults, inflammaging, mitochondrial dysfunction, defective autophagy/mitophagy, and cellular senescence may lower the threshold for persistent inflammasome activation in the vascular wall.
A plain-English summary is on its way. Until then, this is the start of the authors' own summary.
- Who it was tested in
- People
- Kind of research
- A summary of earlier studies
The science
- Original title
- Modulating the NLRP3/IL-1β Axis in Age-Related Atherosclerosis: Natural Products, Molecular Mechanisms, and Translational Perspectives-A Narrative Review.
- Authors
- Marakhovskaya YA, Eruslanova KA, Maltseva ON et al.
- Journal
- Biomolecules
- Published
- Oct 27, 2026
- Study type
- Review · in humans
- PMID
- 42939664 ↗
Abstract
Atherosclerosis is an age-related immune-metabolic disease in which lipid retention, endothelial dysfunction, innate immune activation, and vascular remodeling interact over decades. In older adults, inflammaging, mitochondrial dysfunction, defective autophagy/mitophagy, and cellular senescence may lower the threshold for persistent inflammasome activation in the vascular wall. The NLR family pyrin domain containing 3 (NLRP3) inflammasome and interleukin-1β (IL-1β) are central to this process because they convert sterile danger signals, including cholesterol crystals, oxidized lipids, mitochondrial stress, and disturbed flow, into caspase-1 activation, IL-1β and interleukin-18 (IL-18) maturation, pyroptosis, endothelial dysfunction, macrophage activation, and plaque destabilization. Clinical proof-of-concept from IL-1β blockade supports inflammatory targeting in atherosclerotic cardiovascular disease, but direct cytokine inhibition leaves upstream inflammasome-prone states insufficiently addressed. This narrative review synthesizes evidence published from 2010 to 2026, together with older landmark studies, on mechanistic, translational, and clinical links between the NLRP3/IL-1β axis and age-related atherosclerosis. Traditional Chinese medicine-derived formulas and isolated natural compounds are considered because they may modulate upstream priming, mitochondrial reactive oxygen species, autophagy, lipid handling, macrophage polarization, endothelial pyroptosis, and inflammasome-associated cytokine release. However, most data remain preclinical, and translation requires stronger causal validation, chemical standardization, pharmacokinetic characterization, age-relevant models, and systematic safety assessment.
Marakhovskaya YA, Eruslanova KA, Maltseva ON et al. Modulating the NLRP3/IL-1β Axis in Age-Related Atherosclerosis: Natural Products, Molecular Mechanisms, and Translational Perspectives-A Narrative Review. Biomolecules. 2026. doi:10.3390/biom16101409. PMID: 42939664. https://pubmed.ncbi.nlm.nih.gov/42939664/