Authors
Selim Chaib, Larissa G P Langhi Prata, Masayoshi Suda, Andres Sola, Thomas J Mitchell, Zacharias P Anastasiadis, Hawley E Kunz, Jia Nie, Stella G Victorelli, Ricardo Lozano Flores, Moritz Weigl, Shimpei Kawamoto, Ken Uemura, Hyungsoo Kim, Binsheng Wang, Christina L Inman, Tamar Pirtskhalava, Nino Giorgadze, Ailing Xue, Kurt O Johnson, Jair M Espindola-Netto, Sonja Suvakov, Jennet Hatamova, Erik S Parker, Davyn Benitto Hartono, Vagisha Kulshreshtha, Jose Alberto Lopez-Dominguez, Aaron M Deisinger, Allyson K Palmer, Yi Zhu, Megan M Weivoda, Anne Gingery, Robert Hromas, Vesna D Garovic, João F Passos, David B Allison, Eiji Hara, Michael D Jensen, Nicolas Musi, Stefan G Tullius, Ze'ev A Ronai, Manuel Serrano, Ming Xu, Ian R Lanza, Yuji Ikeno, Tamara Tchkonia, James L Kirkland
Published in
Cell metabolism. Sep 10, 2026. Epub Sep 10, 2026.
Abstract
Senescent cells, which are normally cleared by the immune system but accumulate with age, contribute to multiple disorders including metabolic dysfunction and impaired fitness. While immune checkpoint inhibitors have been well studied in cancer, the role of programmed cell death ligand 2 (PD-L2) in non-cancerous, age-associated cellular senescence remains unclear. We found that PD-L2 is upregulated in isolated senescent human cells and during aging, and senolytics can remove age-associated, highly PD-L2-expressing senescent cells. Old PD-L2 knockout mice accumulate fewer senescent cells than old wild-type mice, and their insulin sensitivity and grip strength are greater. Anti-PD-L2 therapy restored insulin sensitivity in aged wild-type mice. PD-L2 acts as an immune checkpoint on senescent cells, allowing them to evade immune clearance and promoting their persistence during aging. Targeting PD-L2 in senescent cells may be a strategy for alleviating the age-related dysfunction associated with cellular senescence.
PMID:
42721966
Bibliographic data and abstract were imported from PubMed on 11 Sep 2026.
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