What this means
Researchers found that apelin-13 helped brain cells resist aging signs by restoring their cleanup process. This work was done in cells and mice, so it does not show the same effect in people.
Plain-English summary written by an AI model from the abstract. The original is below.
- Who it was tested in
- Human brain cells in a lab, stem-cell-derived brain cells, and aging mice
- Kind of research
- A study
The science
- Original title
- Apelin-13 prevents GATA4-mediated neuronal senescence by restoring autophagy through mTORC1 inhibition.
- Authors
- Han SJ, Cho JH, Lim JR et al.
- Journal
- Cell death & disease
- Published
- Oct 22, 2026
- Study type
- Study · in humans
- PMID
- 42907440 ↗
Abstract
Neuronal senescence, triggered by oxidative stress and inflammatory responses, is a significant risk factor for brain aging, ultimately leading to cognitive decline. Apelin-13, an exercise-induced myokine, exhibits potential neuroprotective effects by the APJ system, but its protective effects against neuronal senescence and the underlying mechanisms are unknown. This study aimed to elucidate how apelin-13 prevents D-galactose-induced neuronal senescence in SH-SY5Ys, human induced pluripotent stem cell-derived neuronal differentiated cells (iPSC-NDs), and an aging mouse model. The administration of ML233, an apelin receptor APJ agonist, attenuated brain aging and cognitive impairment in D-galactose-induced aging mice. In vitro findings showed that apelin-13 failed to scavenge the excessively generated D-galactose-induced reactive oxygen species (ROS) but prevented aging through APJ-Gαq-mediated signaling in SH-SY5Y cells. Apelin-13 activated protein kinase C (PKC) and calmodulin-dependent protein kinase II (CaMKII) to phosphorylate AMPK, which led to the inhibition of mammalian target of rapamycin complex 1 (mTORC1). Inhibition of mTORC1 promoted the nuclear translocation of transcription factor EB (TFEB), restoring lysosomal function and autophagic flux impaired by D-galactose. Furthermore, D-galactose treatment increased the expression of GATA binding protein 4 (GATA4), a transcription factor that contributes to paracrine senescence by increasing the expression of pro-inflammatory cytokines. Neuronal autophagy restored by apelin-13 promoted GATA4 clearance, ultimately preventing pro-inflammatory cytokine-induced paracrine senescence under D-galactose conditions. Collectively, these results demonstrate that apelin-13 prevents neuronal senescence by inhibiting the mTORC1-GATA4 axis through the restoration of autophagy. Our study highlights apelin-13 as a promising therapeutic candidate for age-related cognitive decline by targeting the oxidative stress-inflammation-neuronal senescence axis through the modulation of autophagy.
Han SJ, Cho JH, Lim JR et al. Apelin-13 prevents GATA4-mediated neuronal senescence by restoring autophagy through mTORC1 inhibition. Cell death & disease. 2026. doi:10.1038/s41419-026-09121-1. PMID: 42907440. https://pubmed.ncbi.nlm.nih.gov/42907440/
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