LongeCityNews Last Updated: 18 February 2026 - 03:13 PM

Atherosclerosis is the largest cause of human mortality, a growth of fatty plaques in blood vessel walls that narrow and weaken vessels. The structure and composition of plaques can vary considerably between people and within one individual. The most dangerous plaques are those with more fat and less structural material, as these are prone to rupture, leading to a downstream blockage and a heart attack or stroke. A plaque is a toxic environment that draws in macrophage cells that attempt to repair the lesion, but instead are overwhelmed, killed, and add their mass to the plaque. Initially, circulating monocyte cells arrive at a plaque and turn into macrophages, but in later stages an almost cancerous process causes smooth muscle cells in the vascular wall to turn into macrophages to further accelerate plaque growth and instability. Here, researchers find a way to potentially interfere in this process, and thus greatly reduce the formation of unstable plaques that are prone to rupture.

Smooth muscle cells (SMCs) exhibit remarkable plasticity, undergoing extensive phenotypic switching to generate a highly heterogeneous population within atherosclerotic plaques. While recent studies have highlighted the contribution of SMC-derived macrophage-like cells to plaque inflammation, the specific molecular drivers governing the transition to these pathogenic states remain poorly understood.

Here, we re-analyzed single-cell RNA sequencing data from lineage-traced mice to dissect SMC heterogeneity during atherogenesis. Trajectory analysis revealed that SMCs transdifferentiate into a distinct pro-inflammatory macrophage-like subpopulation via an intermediate "stem-endothelial-monocyte" cell state. Integrated gene regulatory network inference and in silico perturbation modeling identified interferon regulatory factor 7 (IRF7) as a master transcriptional regulator orchestrating this specific pathogenic transition.

Clinically, IRF7 expression was significantly upregulated in unstable and advanced human atherosclerotic plaques, correlating strongly with inflammatory macrophage burden. In vivo, ApoE knockout mice challenged with a high-fat diet exhibited robust upregulation of IRF7 in aortic plaques, which co-localized with macrophage markers. Crucially, SMC-specific knockdown of Irf7 significantly attenuated atherosclerotic plaque progression, reduced necrotic core formation, and enhanced fibrous cap stability. Mechanistically, Irf7 silencing preserved the contractile SMC phenotype and inhibited the accumulation of pro-inflammatory SMC-derived macrophage-like cells within the lesion.

Link: https://doi.org/10.1093/pcmedi/pbaf039

The creation of engineered immune cells equipped with what are known as chimeric antigen receptors (CARs) can in principle be used to target any distinctive population of cells or extracellular materials for selective destruction. First introduced as a treatment for leukemia, this remains a very expensive form of therapy, and so is not as widely developed for new uses as might otherwise be the case. Nonetheless, a steady stream of proof of concept studies exists, such as the example here in which CAR technology is applied to target protein aggregates in the context of Alzheimer's disease.

Alzheimer's disease (AD) is the prevailing cause of age-associated dementia worldwide. Current standard of care relies on antibody-based immunotherapy. However, antibody-based approaches carry risks for patients, and their effects on cognition are marginal. Increasing evidence suggests that T cells contribute to AD onset and progression. Unlike the cytotoxic effects of CD8+ cells, CD4+ T cells capable of regulating inflammation show promise in reducing pathology and improving cognitive outcomes in mouse models of AD and in aging.

Here, we sought to exploit the beneficial properties of CD4+ T cells while circumventing the need for T cell receptor and peptide / major_histocompatibility_complex antigen discovery, thereby providing a potential universal therapeutic approach. To achieve this, we engineered CD4+ T cells with chimeric antigen receptors (CARs) targeting fibrillar forms of aggregated amyloid-β. Our findings demonstrate that optimized CAR-T cells can alter amyloid deposition in the dura and reduce parenchymal pathology in the brain. Furthermore, we observed that CAR-T treatment promotes the expansion and recruitment of endogenous CD4+ T cells into the brain parenchyma and leptomeninges.

In summary, we established the feasibility of amyloid plaque-specific CAR-T cells as a potential therapeutic avenue for AD. These findings highlight the potential of CD4+ CAR-T therapy not only to modify amyloid pathology but also to reshape the immune landscape of the central nervous system, paving the way for future development of cellular immunotherapies for neurodegenerative disease.

Link: https://doi.org/10.1073/pnas.2530977123

The retina at the back of the eye is the one part of the central nervous system that can be readily visually inspected, including the state of the network of blood vessels that supports it. Capillary networks of tiny blood vessels are dense and actively maintained; as the character of angiogenesis changes for the worse with aging, these networks become less dense and exhibit other signs of damage. Thus imagery of the retina provides a lot of data that can be employed to, for example, produce aging clocks, or act as a proxy measure for other forms of vascular and nervous system aging.

For retinal imagery to be usefully employed as a proxy measure of any specific aspect of vascular aging or central nervous system aging, or specific form of age-related damage, a robust correlation must first be demonstrated. Thus we have papers such as today's example, in which researchers establish links between retinal imagery characteristics and vascular and brain aging. One might expect this to inform efforts to further advance retinal imaging as a relatively low cost diagnostic tool, a way to better establish risk and the need for more costly forms of assessment in older people.

Cross-organ analysis reveals associations between vascular properties of the retina, the carotid and aortic arteries, and the brain

Doctors often use eye scans to check for signs of heart and brain disease, but the exact link between the tiny blood vessels in the eye and those in major organs is unclear. We aimed to systematically map similarities between blood vessels across the entire body. We compared vascular image-derived phenotypes from the brain, carotid artery, aorta, and retina, using UK Biobank sample sizes ranging from 18,808 to 68,740 participants. We examined phenotypic and genetic correlations, as well as common associated genes and pathways.

Here we show that white matter hyperintensities are positively correlated with carotid intima-media thickness (r = 0.03), lumen diameter (r = 0.14), and aortic cross-sectional areas (r = 0.09), but negatively correlated with aortic distensibilities (r ≤ -0.05). Arterial retinal vascular density shows negative correlations with white matter hyperintensities (r = -0.04), intima-media thickness (r = -0.04), lumen diameter (r = -0.06), and aortic areas (r = -0.05), while positively correlating with aortic distensibilities (r = 0.04). Significant correlations also persist after correcting for hypertension.

In summary, we found strong connections with the health of retinal blood vessels mirroring the health of the brain and major arteries. This suggests that some of the same factors influence vessel health across the body. This suggests that an eye scan could be a fast, non-invasive way to get a complete snapshot of a person's overall cardiovascular and brain health. These findings could help doctors identify health issues, such as early artery stiffness or brain aging, much sooner.

Scientists have pitted five diets against each other to see which one is associated with more years of life gained [1].

The clash of the diets

Unhealthy eating is recognized as a globally leading cause of death [2]. Surprisingly, few studies have actually evaluated the gains in life expectancy associated with adherence to a healthy diet. In a new study published in Science Advances, an international group of scientists pitted five leading dietary practices against each other using data from UK Biobank, a huge repository of health-related information on hundreds of thousands of British citizens.

The sample was comprised of 103,649 participants (mean age 58.3 years, 56.4% female) who had completed two or more web-based 24-hour dietary assessments and were free of cardiovascular disease (CVD) and cancer at baseline. Each participant was scored on five dietary pattern indices based on what they reported eating: Alternate Healthy Eating Index (AHEI-2010), Alternate Mediterranean Diet (AMED), healthful Plant-based Diet Index (hPDI), Dietary Approaches to Stop Hypertension (DASH), and Diabetes Risk Reduction Diet (DRRD).

Each score was divided into quintiles. The five scores were moderately-to-highly intercorrelated, meaning that the dietary patterns they capture are often overlapping (which is expected), but not identical. The model was adjusted for race, education, socioeconomic deprivation, smoking status, physical activity, BMI, total energy intake, baseline dyslipidemia, hypertension, diabetes, and, for hPDI, DASH, and DRRD, alcohol consumption.

The researchers also wanted to see how dietary patterns interact with known longevity gene variants. They calculated a longevity polygenic risk score (PRS) from 19 single nucleotide polymorphisms (SNPs) which were significantly associated with longevity in a genome-wide association study (GWAS). This model was additionally adjusted for ten genetic principal components.

The winners and the losers

DRRD showed the strongest association with longevity, as the top quintile had 24% lower mortality than the bottom quintile. The authors attribute this to the fact that DRRD’s scoring algorithm directly includes dietary fiber and glycemic index, the two components that individually showed the strongest associations with mortality: fiber was protective, while high glycemic index was detrimental. Product-wise, sugar-sweetened beverages turned out to be the most harmful, in line with previous research [3].

Other scores followed DRRD closely, with 20% reductions in mortality for the top quintiles of AHEI and AMED compared to the bottom ones, 19% for DASH, and 18% for hPDI. Interestingly, noticeable sex-related differences were observed. When the researchers looked at life expectancy, the top performer for men was DRRD, with 3 years gained between the lowest and the highest quintiles, while for women, it was AMED, with 2.3 years. For both sexes, the least effective diet was hPDI (1.9 and 1.5 years, respectively).

How do “longevity genes” factor in?

The team then analyzed PRS’ association with remaining life expectancy, and it turned out to be slightly lower: 1.4 years for men and 1.7 years for women. However, the PRS was split into tertiles, so the researchers compared the top and bottom tertiles. Importantly, the effects of diet and genetics were roughly additive, with DRRD showing the largest combined gains in both sexes. Being both in the top DRRD quintile and in the top PRS tertile was associated with 3.2 years of additional life expectancy for men and 5.5 years for women.

However, the combined estimates are peculiarly noisy, especially for men. For instance, having a top AMED score and a top PRS gives only 1 year for men, which is actually less than either diet alone (2.2) or PRS alone (1.4). This is probably because the combined estimates come from much smaller slices of the cohort, resulting in noise, rather than due to any negative interaction. The women’s combined numbers behave more sensibly and are roughly additive.

Crucially, these estimates are for a 45-year-old person. The life expectancy benefits of switching to a better diet, naturally, diminish with age, as fewer years remain for the risk reduction to play out, while the risk of dying from something unrelated to diet increases.

While this is a well-executed and carefully sensitivity-tested observational study, a few caveats apply. The effect sizes are modest, and the confidence intervals are wide enough for the true benefit to be as small as about 0.5 years in some comparisons. These are also best-case comparisons that compare top and bottom quintiles, while most people usually do not switch their diets from the worst to the best. Finally, the PRS interaction story is intriguing but might not be statistically robust, leaving room for further research.

Literature

[1] Lv, Y., Song, J., Ding, D., Luo, M., He, F. J., Yuan, C., MacGregor, G. A., Liu, L., & Chen, L. (2026). Healthy dietary patterns, longevity genes, and life expectancy: A prospective cohort study. Science advances, 12(7), eads7559.

[2] Afshin, A., Sur, P. J., Fay, K. A., Cornaby, L., Ferrara, G., Salama, J. S., … & Murray, C. J. (2019). Health effects of dietary risks in 195 countries, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. The lancet, 393(10184), 1958-1972.

[3] Imamura, F., O’Connor, L., Ye, Z., Mursu, J., Hayashino, Y., Bhupathiraju, S. N., & Forouhi, N. G. (2015). Consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice and incidence of type 2 diabetes: systematic review, meta-analysis, and estimation of population attributable fraction. Bmj, 351.