PGAM1-Chk1 interaction as a novel target for senolysis to preserve resilience during aging

Takumi Mikawa

Masahiro Kameda

Zexin Zhang

Hiroshi Kondoh

1,*

*Correspondence to: Hiroshi Kondoh, Geriatric Unit, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan. E-mail: hkondoh@kuhp.kyoto-u.ac.jp

Geromedicine. 2026;2:202625. 10.70401/Geromedicine.2026.0034

Received: April 9, 2026Accepted: August 17, 2026Published: August 17, 2026

This manuscript is made available in its unedited form to allow early access to the reported findings. Further editing will be completed before final publication. As such, the content may include errors, and standard legal disclaimers are applicable.

Abstract

Aging is a complex biological process, which is affected by several factors, lifestyle, diet, genetic or epigenetic factors, environmental stress, and metabolisms. Among others, several reports observed increased glycolysis in senescent cells (SnCs) and individual aging, whose causal effects or biological mechanisms have been unclear. Recently, we identified PGAM1-Chk1 binding as a booster for glycolytic metabolism and cell viability in SnCs. Secretary phenotype of inflammatory factors, known as SASP (senescence associated secretary phenotype), is one of prominent properties in SnCs, which accelerates chronic inflammation and aging-relevant dysfunctions in tissues. Inhibition of PGAM1-Chk1 binding removes SnCs and suppresses SASP, alleviating organ damages and pulmonary fibrosis in vivo. Thus, PGAM1-Chk1 interaction; represents a novel target for senolysis to preserve resilience in aging.

Keywords

Resilience, SASP, senolysis, glycolysis, PGAM1, Chk1, HIF-2α, FoxM1

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Mikawa T, Kameda M, Zhang Z, Kondoh H. PGAM1-Chk1 interaction as a novel target for senolysis to preserve resilience during aging. Geromedicine. 2026;2:202625. https://doi.org/10.70401/Geromedicine.2026.0034