Abstract: SA-PO0033
Epigenetically Active Small Molecules Reprogram Renal Progenitor Senescence Through Distinct Epigenetic Signatures
Session Information
- Development, Stem Cells, and Regenerative Medicine
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 700 Development, Stem Cells, and Regenerative Medicine
Authors
- Sallustio, Fabio, Universita degli Studi di Bari Aldo Moro, Bari, Apulia, Italy
- Picerno, Angela, Universita degli Studi di Bari Aldo Moro, Bari, Apulia, Italy
- Cicirelli, Antonella, Universita degli Studi di Bari Aldo Moro, Bari, Apulia, Italy
- Nigro, Alessio, Universita degli Studi di Bari Aldo Moro, Bari, Apulia, Italy
- Montenegro, Francesca, Universita degli Studi di Bari Aldo Moro, Bari, Apulia, Italy
- Giannuzzi, Francesca, Universita degli Studi di Bari Aldo Moro, Bari, Apulia, Italy
- Ladisa, Giorgio, Universita degli Studi di Bari Aldo Moro, Bari, Apulia, Italy
- De Palma, Giuseppe, IRCCS Istituto Tumori "Giovanni Paolo II" Bari, Bari, Italy
- Franzin, Rossana, Universita degli Studi di Bari Aldo Moro, Bari, Apulia, Italy
- Stasi, Alessandra, Universita degli Studi di Bari Aldo Moro, Bari, Apulia, Italy
- Fiorentino, Marco, Universita degli Studi di Bari Aldo Moro, Bari, Apulia, Italy
- Pontrelli, Paola, Universita degli Studi di Bari Aldo Moro, Bari, Apulia, Italy
- Gesualdo, Loreto, Universita degli Studi di Bari Aldo Moro, Bari, Apulia, Italy
Background
Loss of renal progenitor cell (RPC) fitness is a hallmark of kidney aging and may limit repair after injury. Epigenetically active small molecules, including 10-hydroxy-2-decenoic acid (10-HDA), nonanoic acid (NA), and valproic acid (VPA), may modulate aging-related pathways, but their impact on RPC senescence and epigenetic regulation remains incompletely defined.
Methods
Four independent adult RPC lines were exposed to 10-HDA, NA, VPA, or selected combinations. Senescence was evaluated by cell-cycle inhibitors, SA-β-gal activity, SASP cytokines, and progenitor/anti-aging markers including CD133, HOTAIR and α-Klotho. Genome-wide methylation was assessed with the Illumina EPIC BeadChip and analyzed across promoters, gene bodies, CpG islands and 5-kb tiling regions using RnBeads, followed by gProfiler annotation.
Results
10-HDA and NA blunted multiple senescence features, reduced inflammatory SASP signals, and preserved CD133, HOTAIR and α-Klotho expression, supporting a senomorphic effect in RPCs. VPA also decreased senescence and SASP markers, but failed to maintain α-Klotho, suggesting a less complete protective profile. Methylome profiling revealed non-overlapping modes of epigenetic remodeling. 10-HDA generated a balanced bidirectional signature involving 967 differentially methylated regions and 664 genes, with repression of TGF-β/Wnt/Hippo and mTOR/PI3K-related programs. NA induced a hypermethylation-dominant response, involving 572 DMRs and 414 genes, enriched for immune/MHC and lipid-metabolism pathways. VPA caused the widest epigenetic shift, with 1,269 DMRs and 946 genes, consistent with broad chromatin remodeling. CDH12 emerged as a shared hypomethylated target across all treatments.
Conclusion
Epigenetically active small molecules counteract RPC senescence through distinct but complementary programs. 10-HDA appears to restrain pro-senescent growth-factor and nutrient-sensing pathways, whereas NA preferentially remodels immune and metabolic circuits. These data support 10-HDA and NA as candidate senomorphic agents to preserve renal progenitor function during kidney aging.
Acknowledgment
This study received funding from the European Union—Next-GenerationEU—National Recovery and Resilience Plan (NRRP)—Mission 4 Component 2, Investiment N. 1.1, Call PRIN 2022 PNRR D.D. 1409 14-09-2022: P2022W5N2X—Aging and Decline of Renal Progenitor Regenerative Capacity: Identification of Molecular Mechanisms and Anti-Senescent Molecules as Therapeutic Treatments for CKD.
Funding
- Government Support – Non-U.S.