bims-nimamd Biomed News
on Neuroimmunity and neuroinflammation in ageing and metabolic disease
Issue of 2026–07–05
24 papers selected by
Fawaz Alzaïd, Sorbonne Université
  1. A spatial atlas of pancreatic remodelling in type 1 diabetes.
  2. Maternal IFN shapes neurodevelopment.
  3. Epigenetic mechanisms of inflammatory memory in the central nervous system.
  4. Age-related molecular changes that are exercise independent.
  5. The interplay between the microbiome and immune cells in metabolic homeostasis and disease.
  6. Local signals, systemic decline.
  7. Inhibition of telomere damage signaling restores hematopoiesis and immune function.
  8. Critical connections.
  9. Eosinophils are mothers' helpers.
  10. Embryonic senescence.
  11. A carboxylate switch point controls long-range energy transduction in respiratory Complex I.
  12. Dementia risk in middle-aged people linked to a blood protein.
  13. US Dietary Supplement Use Increasing, Especially in Older Adults.
  14. Genetic Determinants of Macronutrient Intake Are Associated With Specific Food Intake in Youth: A Cohort Study Across Childhood and Adolescence.
  15. Assessing the effect of immune surveillance on clonal expansions in the blood.
  16. Sustained A2AR expression and loss paradoxically promote CD8+ T cell exhaustion.
  17. Liver fat steers the outcome of advanced colorectal cancer.
  18. Mitochondrial quality control in human ageing and longevity.
  19. Why high scores do not mean application readiness for health AI.
  20. A Non-Canonical Role for Hepatocyte MLKL in Promoting Mitochondrial Dysfunction and Senescence in the Aging Liver.
  21. Pyruvate leaves its mark on chromatin.
  22. Transposable elements impact the human regulatory landscape through cell type specific epigenomic associations.
  23. The complex truth about trust in science.
  24. FDA Adds Kidney Injury Warning to OTC Weight-Loss Drug Orlistat.
  1. Nat Metab. 2026 Jul 02.
    A spatial atlas of pancreatic remodelling in type 1 diabetes.
    Carson Mickey, Yue J Wang.
      
    DOI:  https://doi.org/10.1038/s42255-026-01547-3
  2. Nat Immunol. 2026 Jul;27(7): 1316
    Maternal IFN shapes neurodevelopment.
    Stephanie Houston.
      
    DOI:  https://doi.org/10.1038/s41590-026-02588-2
  3. Nat Immunol. 2026 Jul;27(7): 1336-1352
    Epigenetic mechanisms of inflammatory memory in the central nervous system.
    Jessica J Ye, Francisco J Quintana.
      Inflammatory memory enables cells to remember prior inflammatory signals, shaping their responses to subsequent challenges. While this phenomenon has been extensively characterized in immune cells and various tissues, recent reports suggest that both immune and nonimmune cells in the central nervous system (CNS) also exhibit inflammatory memory. In this Perspective, we synthesize emerging evidence of inflammatory memory in the CNS and discuss its underlying mechanisms. We highlight how epigenomic reprogramming through histone and DNA modifications, the recruitment of epigenetic regulators and nucleosome remodeling drive changes in gene expression kinetics central to inflammatory memory. We also examine mechanisms that maintain or reset inflammatory memory. By identifying shared principles and CNS-specific features, we propose conceptual frameworks to advance our understanding of CNS inflammatory memory and its implications for health and disease.
    DOI:  https://doi.org/10.1038/s41590-026-02541-3
  4. Nat Aging. 2026 Jul 03.
    Age-related molecular changes that are exercise independent.
      
    DOI:  https://doi.org/10.1038/s43587-026-01157-4
  5. Cell Metab. 2026 Jun 29. pii: S1550-4131(26)00230-5. [Epub ahead of print]
    The interplay between the microbiome and immune cells in metabolic homeostasis and disease.
    Hagit Shapiro, Birgit Jickeli, Idan Niv, Ben Ernan, Eran Elinav.
      Microbiome-derived metabolites, including short-chain fatty acids, bile acids, indoles, and lipopolysaccharides, among other bioactives, modulate mammalian immune cells through a variety of molecular processes, including epigenetic remodeling, mitochondrial metabolic reprogramming, and regulation of mTOR and AMPK signaling pathways. These diverse signals shape inflammatory programs that influence metabolic outcomes in a context-dependent manner, which may sustain metabolic health or drive chronic inflammation impacting obesity, type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, and cardiovascular diseases. Here, we review these metabolite-driven immune-metabolic influences and highlight innovative directions in their exploration, including integration of spatial and single-cell multi-omics to deconvolute microbiome-derived signaling networks within metabolic tissues. We further outline emerging microbiome-based therapeutic strategies targeting immune pathways in cardiometabolic disease, ranging from personalized nutrition, precision probiotics, and microbial consortium transplantation to metabolite-based postbiotics. Collectively, advancing our understanding of host immune-microbiome-metabolic interactions may support the development of targeted interventions for the prevention and treatment of cardiometabolic diseases.
    Keywords:  immune system; metabolism; metabolites; microbiome; microbiota; obesity
    DOI:  https://doi.org/10.1016/j.cmet.2026.06.004
  6. Science. 2026 Jul 02. 393(6806): 33-34
    Local signals, systemic decline.
    Yetiş Gültekin, Matthew G Vander Heiden.
      A high-fat diet affects tumor-to-nerve signaling and promotes cachexia in mice.
    DOI:  https://doi.org/10.1126/science.aej0415
  7. Nat Aging. 2026 Jun 30.
    Inhibition of telomere damage signaling restores hematopoiesis and immune function.
      
    DOI:  https://doi.org/10.1038/s43587-026-01146-7
  8. Nat Immunol. 2026 Jul;27(7): 1311
    Critical connections.
      
    DOI:  https://doi.org/10.1038/s41590-026-02594-4
  9. Nat Immunol. 2026 Jul;27(7): 1316
    Eosinophils are mothers' helpers.
    Laurie A Dempsey.
      
    DOI:  https://doi.org/10.1038/s41590-026-02587-3
  10. Nat Immunol. 2026 Jul;27(7): 1316
    Embryonic senescence.
    Ioana Staicu.
      
    DOI:  https://doi.org/10.1038/s41590-026-02589-1
  11. Nat Commun. 2026 Jul 01. pii: 5737. [Epub ahead of print]17(1):
    A carboxylate switch point controls long-range energy transduction in respiratory Complex I.
    Adel Beghiah, Patricia Saura, Terezia Kovalova, Franziska Hoeser, Thorsten Friedrich, Ville R I Kaila.
      Complex I is a highly intricate membrane-bound protein complex that powers the cellular energy metabolism by a long-range ( > 300 Å) proton-coupled electron transfer (PCET) reaction. Here, we investigate the highly debated coupling mechanism of Complex I by probing the charge transfer reaction along its functionally central carboxylate pathway (E-channel). By combining biophysical and site-directed mutagenesis experiments with high-resolution (2.6-2.8 Å) cryo-electron microscopy (cryo-EM) and multiscale simulations, we identify a conserved carboxylate switch point (D79NuoA) that mediates proton transfer by establishing a kinetic gate and couples the redox chemistry to proton pumping. We find that mutation of the identified site, as found in patients suffering from severe neurodegenerative disorders, drastically perturbs the charge transfer mechanism, and results in a 20% PCET activity. Our combined findings illustrate mechanistic principles of molecular gates underlying long-range charge transfer reactions, and show how disease mutations perturb the function of conserved switch points in energy transduction.
    DOI:  https://doi.org/10.1038/s41467-026-74767-6
  12. Nature. 2026 Jun 26.
    Dementia risk in middle-aged people linked to a blood protein.
      
    Keywords:  Neurodegeneration
    DOI:  https://doi.org/10.1038/d41586-026-02035-0
  13. JAMA. 2026 Jul 02.
    US Dietary Supplement Use Increasing, Especially in Older Adults.
    Samantha Anderer.
      
    DOI:  https://doi.org/10.1001/jama.2026.9466
  14. Diabetes Care. 2026 Jun 29. pii: dc252975. [Epub ahead of print]
    Genetic Determinants of Macronutrient Intake Are Associated With Specific Food Intake in Youth: A Cohort Study Across Childhood and Adolescence.
    Soren Harnois-Leblanc, Jenny M Brown, Karen M Switkowski, Izzuddin M Aris, Sheryl L Rifas-Shiman, Emily Oken, Julie E Gervis, Kenneth Westerman, Hassan S Dashti, Marie-France Hivert, Jordi Merino.
       OBJECTIVE: We examined associations of polygenic scores (PS) for macronutrient intake with food intake and cardiometabolic outcomes during childhood and adolescence and evaluated gene enrichment in hypothalamic cell types.
    RESEARCH DESIGN AND METHODS: We derived carbohydrate, fat, and protein intake PS from an adult genome-wide association study among 516 non-Hispanic White children from the Project Viva cohort. We estimated dietary intake and calculated BMI z scores from measured height and weight at ages ∼3, 8, 13, and 18 years. Waist circumference, truncal fat, fasting glucose, insulin, glycated hemoglobin, and blood lipids were measured at 18 years. We estimated associations of PS with sugar-sweetened beverages (SSB), fast food, and BMI z score using generalized estimating equations (longitudinal), and using regression models for cardiometabolic and secondary dietary outcomes (cross-sectional). We evaluated enrichment of macronutrient intake genetic signals in hypothalamic cell types in the Human HYPOMAP data set.
    RESULTS: A 1-SD increase in carbohydrate PS was associated with higher odds of consuming two or more servings per week of SSB (odds ratio [OR] 1.20; 95% CI 1.07, 1.33) and one or more times per week of fast food (OR 1.11; 95% CI 1.004, 1.23) from ages 3 to 18 years. Higher-protein PS was associated with lower odds of consuming SSB (OR 0.84; 95% CI 0.75, 0.93). We did not observe consistent associations between macronutrient intake PS and cardiometabolic outcomes. We observed hypothalamic regional and neurotransmitter-specific patterns of gene enrichment for carbohydrate or protein intake.
    CONCLUSIONS: Genetic susceptibility for carbohydrate intake is associated with SSB and fast-food consumption in youth. Underlying pathways relating to hypothalamic nutrient-specific appetite signaling may be involved.
    DOI:  https://doi.org/10.2337/dc25-2975
  15. Nat Genet. 2026 Jul 01.
    Assessing the effect of immune surveillance on clonal expansions in the blood.
      
    DOI:  https://doi.org/10.1038/s41588-026-02602-1
  16. Proc Natl Acad Sci U S A. 2026 Jul 07. 123(27): e2602385123
    Sustained A2AR expression and loss paradoxically promote CD8+ T cell exhaustion.
    Longzhen Song, Arjun Kharel, Ping Xie, Jie Fan, Abu Baker, Yuqi Zhang, Yi Zhang, Weiguo Cui, Bin Zhang.
      Although A2AR is a key immunoregulatory receptor that suppresses CD8+ T cell activation in response to elevated extracellular adenosine in inflamed or hypoxic microenvironments, its role in CD8+ T cell differentiation and cell-fate decisions during chronic viral infection and cancer remains poorly understood. Using A2AR-eGFP reporter mice, we show that A2AR expression is rapidly induced by TCR stimulation and persists under chronic antigen exposure and hypoxia, with sustained expression strongly associated with terminal exhaustion via the canonical Gαs-cAMP-PKA pathway. Paradoxically, A2AR loss does not alleviate exhaustion but instead accelerates differentiation toward the terminally exhausted state. Single-cell multiomics profiling revealed that A2AR deficiency activates CD122 (IL-2Rβ)-dependent signaling, driving T cell exhaustion. Genetic deletion of CD122 in A2AR-deficient CD8+ T cells reduced terminal exhaustion, identifying CD122 signaling as a key mediator of A2AR loss-driven exhaustion. Intriguingly, both sustained A2AR expression and A2AR loss converge to promote T cell exhaustion differentiation through distinct mechanisms. These findings uncover a paradoxical role of A2AR in shaping CD8+ T cell fate choices during chronic infection and cancer.
    Keywords:  A2AR; CD8(+) T cell differentiation; exhaustion; immunotherapy
    DOI:  https://doi.org/10.1073/pnas.2602385123
  17. Nature. 2026 Jul 01.
    Liver fat steers the outcome of advanced colorectal cancer.
      
    Keywords:  Cancer; Metabolism
    DOI:  https://doi.org/10.1038/d41586-026-01747-7
  18. Nat Metab. 2026 Jun 29.
    Mitochondrial quality control in human ageing and longevity.
    Anna Picca, Luigi Ferrucci.
      Mitochondria play central roles in cellular metabolism and in key processes such as inflammation, stress response, cell death and signalling. Mitochondrial quality control (MQC) mechanisms continuously monitor organelle integrity and function, and repair or eliminate damaged mitochondria to replace them with newly formed, healthy organelles. MQC is particularly important under metabolic or environmental stress conditions. Failure of MQC paves the way to chronic diseases, such as diabetes, metabolic syndromes and immunosenescence. This Review summarizes our current understanding of MQC biology in the context of healthy human longevity. We explore the regulation of MQC in physiological conditions and explain how the dysregulation of MQC in ageing negatively impacts systemic metabolism and immune function. We discuss emerging therapeutic strategies-such as NAD+, AMPK activators and caloric restriction-that maintain a robust MQC to improve metabolic resilience and illustrate how preclinical and clinical studies can leverage MQC as a potential gerotherapeutic target.
    DOI:  https://doi.org/10.1038/s42255-026-01563-3
  19. Nat Med. 2026 Jul 02.
    Why high scores do not mean application readiness for health AI.
      
    DOI:  https://doi.org/10.1038/s41591-026-04500-9
  20. Aging Cell. 2026 Jul;25(7): e70618
    A Non-Canonical Role for Hepatocyte MLKL in Promoting Mitochondrial Dysfunction and Senescence in the Aging Liver.
    Sabira Mohammed, Chao Jiang, Travis Pennington, Shylesh Bhaskaran, Phoebe Ohene-Marfo, Kara F Kneuper, Constantin Georgescu, Kamille Pitts, Albert Tran, Zongkai Peng, Amit Singh, Zhibo Yang, Tiangang Li, Bethany Hannafon, Courtney Houchen, Jonathan D Wren, Andriy Yabluchanskiy, Veronica Galvan, Nagib Ahsan, Michael Kinter, Tommy L Lewis, Sathyaseelan S Deepa.
      Liver aging is characterized by chronic inflammation and metabolic dysfunction that drive progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Necroptosis, a pro-inflammatory form of cell death via the Receptor-Interacting serine/threonine-Protein Kinase 1 (RIPK1)-RIPK3-Mixed Lineage kinase domain Like pseudokinase (MLKL) pathway, is activated in aging livers, and systemic inhibition of this pathway reduces hepatic inflammation and pathology. The cell type-specific role of necroptosis in liver aging, however, is unclear. Notably, RIPK3 is suppressed in hepatocytes under metabolic disease, suggesting necroptosis independent functions for MLKL. Here, we show that MLKL is elevated in aged hepatocytes and drives liver aging via a non-necroptotic mechanism. Using hepatocyte-specific MLKL-overexpressing mice (MLKLHepOE), we find that MLKL overexpression does not induce necroptosis but instead promotes cellular senescence, evidenced by increased p16INK4a and p21WAF1/Cip1 and elevated senescence associated secretory phenotype (SASP). Mechanistically, MLKL induces hepatocyte mitochondrial dysfunction, with impaired respiration, altered mitochondrial dynamics, and increased reactive oxygen species, implicating oxidative stress as a contributing mechanism. This mitochondrial stress is associated with enhanced release of pro-inflammatory extracellular vesicles (EVs) and induction of senescence in hepatocytes and non-parenchymal cells. While hepatocytes contribute substantially to total senescent burden by abundance, macrophages emerge as a senescence-enriched population, indicating amplification of senescence through non-cell-autonomous signaling. Collectively, these findings reveal a non-lethal, non-necroptotic function of hepatocyte MLKL in promoting liver inflammaging via mitochondrial dysfunction and paracrine senescence signaling, identifying MLKL as a regulator of hepatic aging and a potential therapeutic target in age-associated liver disease.
    Keywords:  MLKL; aging; fission‐fusion; hepatocyte; liver; mitochondria; oxidative stress; senescence
    DOI:  https://doi.org/10.1111/acel.70618
  21. Nat Metab. 2026 Jul 03.
    Pyruvate leaves its mark on chromatin.
    Xin Li, Xiang David Li.
      
    DOI:  https://doi.org/10.1038/s42255-026-01561-5
  22. Nat Commun. 2026 Jul 01.
    Transposable elements impact the human regulatory landscape through cell type specific epigenomic associations.
    Jeffrey Hyacinthe, Guillaume Bourque.
      Transposable elements (TEs) are DNA sequences able to create copies of themselves within the genome. TEs have been shown to act as cis-regulatory elements and be co-opted in the human genome. Thus, their impact might come from their relationship with the epigenome. However, a systematic analysis that relates TEs with chromatin histone marks across human cell types remains lacking. Here we leverage a dataset from the International Human Epigenome Consortium featuring 4867 uniformly processed ChIP-seq experiments for 6 histone marks across 47 cell types and show that TEs have drastically different enrichments levels across histone marks. We find that TEs are generally depleted but enriched in select contexts such as L1s in H3K9me3 histone mark. Notably, we identify 456 cell type-histone-TE triplets with strong cell-type specific enrichments and show that many of these triplets are associated with relevant biological processes.
    DOI:  https://doi.org/10.1038/s41467-026-74920-1
  23. Nature. 2026 Jul;655(8121): 7
    The complex truth about trust in science.
      
    Keywords:  Research data; Research management; Scientific community; Society
    DOI:  https://doi.org/10.1038/d41586-026-01974-y
  24. JAMA. 2026 Jul 02.
    FDA Adds Kidney Injury Warning to OTC Weight-Loss Drug Orlistat.
    Samantha Anderer.
      
    DOI:  https://doi.org/10.1001/jama.2026.9467
This page is being maintained by Thomas Krichel. It was last updated on 2026‒07‒05 at 18:54.