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Updated: Jun 26, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Senescent-like border-associated macrophages regulate cognitive aging via migrasome-mediated induction of paracrine
Mengyan Hu1,2, Xinmei Kang1, Zhiruo Liu1
1Department of Neurology, Mental and Neurological Disease Research Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Abstract:
Aging is a major risk factor for various neurological disorders, including Alzheimer's disease, and is associated with the accumulation of senescent cells, which can themselves propagate the senescence process through paracrine signaling. Migrasomes are organelles that form during cellular migration, detach from parent cells and mediate intercellular communication. Here we demonstrate that border-associated macrophages (BAMs) acquire senescence-associated properties during early brain aging, possibly due to prolonged exposure to amyloid beta. Senescent-like BAMs show elevated production of migrasomes, which convey senescence-associated signals including the apoptosis inhibitor of macrophage to neighboring cells. We show that microglia are prominent recipients of senescent-like BAM-derived migrasomes, and that through activation of CD16 in recipient cells, the apoptosis inhibitor of macrophage inhibits apoptosis and promotes senescence induction. Blocking migrasome induction in senescent-like BAMs through treatment with Tspan4-targeting siRNA-encapsulated liposomes ameliorates cognitive deficits in aged mice. Our findings suggest that migrasomes are potent vehicles of senescence-regulatory signals and represent a promising target for senomorphic therapy.
Insights
Brain aging accelerates with senescent cells. Migrasomes from these cells spread senescence, worsening cognitive decline. Blocking migrasomes improved memory in aged mice, offering a new therapeutic target.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Cellular senescence is a hallmark of aging and a risk factor for neurological disorders like Alzheimer's disease.
- Senescent cells propagate aging through paracrine signaling, involving structures like migrasomes.
- Migrasomes are key mediators of intercellular communication during cell migration.
Purpose of the Study:
- To investigate the role of migrasomes in brain aging and senescence.
- To explore the function of border-associated macrophages (BAMs) in brain aging.
- To identify potential therapeutic targets for age-related cognitive decline.
Main Methods:
- Examined senescence-associated properties of BAMs in aged mice.
- Analyzed migrasome production and content from senescent-like BAMs.
- Investigated the effects of BAM-derived migrasomes on microglia.
- Utilized Tspan4-targeting siRNA-encapsulated liposomes to block migrasome induction.
- Assessed cognitive function in aged mice after treatment.
Main Results:
- BAMs acquire senescence-associated properties in early brain aging, potentially due to amyloid beta exposure.
- Senescent-like BAMs produce migrasomes carrying senescence signals, including the apoptosis inhibitor of macrophage.
- Microglia receive these migrasomes, leading to apoptosis inhibition and senescence induction via CD16 activation.
- Blocking migrasome production ameliorated cognitive deficits in aged mice.
Conclusions:
- Migrasomes are critical mediators of senescence signaling in the aging brain.
- BAM-derived migrasomes contribute to neuroinflammation and cognitive decline.
- Targeting migrasome production represents a promising senomorphic therapy for age-related neurological disorders.
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