ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2018
Macrophage Depletion Ameliorates Peripheral Neuropathy in Aging Mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 69 citations in OpenAlex.
- Aging-Related Changes in the Injury Response of the Peripheral Nervous System.Neuroscience bulletin · 2026Review
- Age-Associated Senescence of Decidual Macrophages: A Key Mediator of Adverse Pregnancy Outcomes in Advanced Maternal Age.Aging cell · 2026Article
- Aging disrupts sympathetic innervation of the thymus.Cell reports · 2026Article
- Aging and Peripheral Nerve Injuries: Impaired Repair, Inflammaging Impact, and Regeneration Resistance.Biomedicines · 2026Review
- Spatiotemporal Remodeling of Presynaptic Terminals in Human Neuromuscular Junctions.International journal of molecular sciences · 2026Article
- Time‑resolved multi-omic analysis of paclitaxel exposure in human iPSC‑derived sensory neurons unveils mechanisms of chemotherapy‑induced peripheral neuropathy.Cell death & disease · 2026Article
- Article
- Fibroblast growth factor signaling induces a chondrocyte-like state of peripheral nerve fibroblast during aging.Nature communications · 2025Article
- Clinical application of mesenchymal stem cells in immunosenescence: a qualitative review of their potential and challenges.Stem cell research & therapy · 2025Review
- Diverse cell types establish a pathogenic immune environment in peripheral neuropathy.Journal of neuroinflammation · 2025Article
- Physical exercise halts further functional decline in an animal model for Charcot-Marie-Tooth disease 1X at an advanced disease stage.Journal of the peripheral nervous system : JPNS · 2024Article
- Advancements in Targeting Macrophage Senescence for Age-Associated Conditions.Aging and disease · 2024Review
- Older spiny mice (Acomys cahirinus) have delayed and spatially heterogenous ear wound regeneration.Biology open · 2024Article
- Schwann Cells as Orchestrators of Nerve Repair: Implications for Tissue Regeneration and Pathologies.Cold Spring Harbor perspectives in biology · 2024Review
- Macrophage senescence in health and diseases.Acta pharmaceutica Sinica. B · 2024Review
- Review
- Proteomic analysis of peripheral nerve myelin during murine aging.Frontiers in cellular neuroscience · 2023Article
- Osteoarthritis Pain in Old Mice Aggravates Neuroinflammation and Frailty: The Positive Effect of Morphine Treatment.Biomedicines · 2022Article
- Single-cell analysis of skeletal muscle macrophages reveals age-associated functional subpopulations.eLife · 2022Article
- Emerging Role of HDACs in Regeneration and Ageing in the Peripheral Nervous System: Repair Schwann Cells as Pivotal Targets.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aging is known as a major risk factor for the structure and function of the nervous system. There is urgent need to overcome such deleterious effects of age-related neurodegeneration. Here we show that peripheral nerves of 24-month-old aging C57BL/6 mice of either sex show similar pathological alterations as nerves from aging human individuals, whereas 12-month-old adult mice lack such alterations. Specifically, nerve fibers showed demyelination, remyelination and axonal lesion. Moreover, in the aging mice, neuromuscular junctions showed features typical for dying-back neuropathies, as revealed by a decline of presynaptic markers, associated with α-bungarotoxin-positive postsynapses. In line with these observations were reduced muscle strengths. These alterations were accompanied by elevated numbers of endoneurial macrophages, partially comprising the features of phagocytosing macrophages. Comparable profiles of macrophages could be identified in peripheral nerve biopsies of aging persons. To determine the pathological impact of macrophages in aging mice, we selectively targeted the cells by applying an orally administered CSF-1R specific kinase (c-FMS) inhibitor. The 6-month-lasting treatment started before development of degenerative changes at 18 months and reduced macrophage numbers in mice by ∼70%, without side effects. Strikingly, nerve structure was ameliorated and muscle strength preserved. We show, for the first time, that age-related degenerative changes in peripheral nerves are driven by macrophages. These findings may pave the way for treating degeneration in the aging peripheral nervous system by targeting macrophages, leading to reduced weakness, improved mobility, and eventually increased quality of life in the elderly.
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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.