image: Proposed mechanism reviewed in Geromedicine: increased PGAM1-Chk1 binding may support glycolysis, DNA-repair signaling and the survival of senescent cells. The model is based on preclinical evidence and has not been established as a treatment approach in people. Credit: Mikawa et al., Geromedicine (2026), CC BY 4.0. Reuse only after the publisher confirms that all incorporated graphic elements are cleared for EurekAlert! distribution.
Credit: © Takumi Mikawa, Masahiro Kameda, Zexin Zhang, Hiroshi Kondoh* 2026. This is an Open Access article licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
KYOTO, Japan, August 17, 2026 - Senescent cells - cells that have stopped dividing but remain metabolically active - can accumulate with age and contribute to chronic inflammation and tissue dysfunction. A new Mini Review in Geromedicine examines a protein interaction that may help some of these cells survive, highlighting a possible route toward more selective strategies for clearing them.
The review, led by researchers at Kyoto University, focuses on the interaction between phosphoglycerate mutase 1 (PGAM1) and checkpoint kinase 1 (Chk1). The authors describe evidence that this interaction is increased in multiple models of cellular senescence and supports a distinct, heightened form of glucose metabolism in senescent cells. They call this pattern a "pseudo-Warburg effect," distinguishing it from the classic metabolic program seen in rapidly growing cancer cells.
According to the review, the PGAM1-Chk1 interaction can stabilize the transcription factor HIF-2alpha. This is linked to glycolysis, the pentose phosphate pathway and lactate production, as well as to FoxM1-dependent DNA-repair and anti-apoptotic programs. Together, these processes may help senescent cells remain viable despite cellular stress.
The review also discusses prior preclinical work by the authors on Nutlin 3b, one optical isomer of a compound originally developed to affect the p53-MDM2 pathway. In the work summarized, Nutlin 3b disrupted the PGAM1-Chk1 interaction without blocking p53-MDM2 binding, selectively removed senescent cells in experimental systems, and showed an acceptable safety profile in young mice. In aged mouse models, the reported findings included improvement in several age-related dysfunctions and reduced lung fibrosis.
The authors stress that these findings are preclinical. Cellular senescence is heterogeneous across tissues and cell types: the review notes that Nutlin 3b was active against senescent fibroblasts and macrophages in vitro, but not against senescent endothelial cells. Its feasibility in people remains unknown. Before any clinical application, researchers will need to establish pharmacokinetics, long-term safety, dosing, tissue distribution and biomarkers for selecting and monitoring patients.
By bringing metabolic regulation, DNA repair and cell-survival signaling into a single framework, the authors argue that the PGAM1-Chk1 axis may help explain why certain senescent-cell populations persist. The proposed mechanism could guide future research on senolytics - approaches intended to remove senescent cells - while underscoring the need for tissue-specific and safety-focused testing.
Method of Research
Literature review
Subject of Research
Not applicable
Article Title
PGAM1-Chk1 interaction as a novel target for senolysis to preserve resilience during aging
Article Publication Date
17-Aug-2026
COI Statement
The authors declare no conflicts of interest.