Senescent microglia with shortened telomeres secrete soluble DLK1 to induce aging-associated hypomyelination and neuronal dysfunction

Liu B, Gan L

1. 01

   DLK1 identified as a senescence-associated ligand in human iPSC-derived microglia

2. 02

   Telomere-shortened mice show hypomyelination, microglial atrophy and cognitive deficits

3. 03

   Soluble DLK1 rises in CSF of aged and telomere-shortened mice and is abolished by microglial depletion

4. 04

   sDLK1 impairs oligodendrocyte function and alters neuronal activity

5. 05

   DLK1 rises with age in human brain single-cell datasets

Study Design

Preclinical mechanistic study

Sample Size

Not reported

Study Duration

Not reported

Methodology

Human iPSC-derived microglia senescence models, telomere-shortened mouse models, single-nucleus RNA sequencing, microglial depletion, CSF measurement, human single-cell brain data

Limitations

Entirely preclinical apart from human expression data; no anti-DLK1 agent exists for this indication, and no human CSF DLK1 assay is validated for clinical use. Telomere-shortened mice are an accelerated model, not normative aging.