ArticleGeroScience2021
Necroptosis increases with age in the brain and contributes to age-related neuroinflammation.
Article in GeroScience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Uncovering Necroptosis in Alzheimer's Disease: A Systematic Review of Evidence Across Experimental Models.Cellular and molecular neurobiology · 2025Pooled it
- In Situ Photo‑Crosslinked Functional Bilayer Hydrogel Modulates Local Microenvironment and Remyelination After Optic Nerve Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The immunology behind inflammaging-causes, sources, and mechanisms.The Journal of allergy and clinical immunology · 2026Review
- Necroptosis in Down Syndrome.Cell death & disease · 2026Article
- The Central Role of Neuronal Cell Death in Alzheimer's Disease Pathobiology.Biomedicines · 2026Review
- Necroptosis induced by MLKL overexpression in liver triggers cellular senescence and leads to chronic inflammation and fibrosis.GeroScience · 2026Article
- Immune Aging as a Failure of Programmed Cell Death Coordination.International journal of molecular sciences · 2026Review
- Intermittent fasting and immune aging: implications for immunosenescence, inflammaging, neuroinflammation, and frailty.Frontiers in nutrition · 2026Review
- Proteasomal dysfunction in the mouse forebrain induces mitochondrial DNA release, cGAS-STING signaling activation, and necroptosis.Journal of neuropathology and experimental neurology · 2025Article
- Modeling neurodegeneration in the retina and strategies for developing pan-neurodegenerative therapies.Molecular neurodegeneration · 2025Review
- Targeting Gut Microbiota to Combat Vascular Aging and Cardiovascular Disease: Mechanisms and Therapeutic Potential.Nutrients · 2025Review
- Article
- Oxidative Stress in the Regulation of Autosis-Related Proteins.Antioxidants (Basel, Switzerland) · 2025Review
- The role of inflammation induced by necroptosis in the development of fibrosis and liver cancer in novel knockin mouse models fed a western diet.GeroScience · 2025Article
- Therapeutic potential of young plasma in reversing age-related liver inflammation via modulation of NLRP3 inflammasome and necroptosis.Biogerontology · 2025Article
- Microglia programmed cell death in neurodegenerative diseases and CNS injury.Apoptosis : an international journal on programmed cell death · 2025Review
- MLKL-USP7-UBA52 signaling is indispensable for autophagy in brain through maintaining ubiquitin homeostasis.Autophagy · 2025Article
- Advances in the Study of Necroptosis in Vascular Dementia: Focus on Blood-Brain Barrier and Neuroinflammation.CNS neuroscience & therapeutics · 2025Review
- Study on the Therapeutic Effects of Bisdemethoxycurcumin on a Cerebral Amyloid Angiopathy Mouse Model Established via Chronic Treatment With Five Vascular Risk Factors.Brain and behavior · 2025Article
- Hydrogen sulphide alleviates depression-like behaviors by suppressing the hippocampal necroptosis-neuroinflammation-KP imbalance axis.Frontiers in pharmacology · 2025Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Chronic inflammation of the central nervous system (CNS), termed neuroinflammation, is a hallmark of aging and a proposed mediator of cognitive decline associated with aging. Neuroinflammation is characterized by the persistent activation of microglia, the innate immune cells of the CNS, with damage-associated molecular patterns (DAMPs) being one of the well-known activators of microglia. Because necroptosis is a cell death pathway that induces inflammation through the release of DAMPs, we hypothesized that an age-associated increase in necroptosis contributes to increased neuroinflammation with age. The marker of necroptosis, phosphorylated form of MLKL (P-MLKL), and kinases in the necroptosis pathway (RIPK1, RIPK3, and MLKL) showed a region-specific increase in the brain with age, specifically in the cortex layer V and the CA3 region of the hippocampus of mice. Similarly, MLKL-oligomers, which cause membrane binding and permeabilization, were significantly increased in the cortex and hippocampus of old mice relative to young mice. Nearly 70 to 80% of P-MLKL immunoreactivity was localized to neurons and less than 10% was localized to microglia, whereas no P-MLKL was detected in astrocytes. P-MLKL expression in neurons was detected in the soma, not in the processes. Blocking necroptosis using Mlkl
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.