Melissic acid reduces senescence in human stem cells via cAMP signaling
A screen of 800 natural compounds identified a phytochemical that activates autophagy and restores cell-cycle activity in models of cellular exhaustion.
Frontiers in pharmacology · Yang K et al. · Paper published 17 Sep 2026
In cultured human exfoliated deciduous tooth stem cells, researchers identified the phytochemical melissic acid as a candidate to counter cellular senescence. The authors screened 800 natural compounds against replicatively senescent cells and confirmed their findings in both replicative exhaustion and doxorubicin-induced stress models. Melissic acid at 5 to 20 micromolar concentrations demonstrated minimal cytotoxicity and significantly reduced SA-beta-Gal activity alongside other senescence markers. Molecular analyses showed the compound upregulated ADCY5 and stimulated cAMP/CREB signaling, promoting autophagy via increased Beclin-1 and reduced p62. Melissic acid also lowered lipid peroxidation, restored mitochondrial membrane potential, and relieved G0/G1 arrest through Cyclin D1 upregulation and Rb phosphorylation.
Why it matters
The findings show that activating cAMP-dependent autophagy can mitigate stem cell senescence, highlighting melissic acid as a potential senomorphic agent to preserve regenerative capacity.
Caveats
The study was conducted entirely in cell culture models, meaning the compound's safety, bioavailability, and anti-senescence effects in living organisms remain unknown.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
High-throughput phenotypic screening identifies the phytochemical melissic acid that mitigates SHED cellular senescence via the ADCY5/cAMP/CREB axis
Yang K, Liu L, Li C et al.
Frontiers in pharmacology · 17 Sep 2026 · Peer-reviewed
- Relevance
- Core geroscience
- News value
- Notable
- Evidence
- Cells
- Status
- Peer-reviewed
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