Senescent Cell Accumulation and Immune Evasion in Aging [Mar. 25, 2025] 

SGLT2 inhibition eliminates senescent cells and alleviates pathological aging (Nature Aging, 2024)
Sodium–glucose co-transporter 2 (SGLT2) inhibition promotes clearance of senescent cells by enhancing immune surveillance, in part through downregulation of PD-L1. This indirect senolytic effect ameliorates age-related metabolic dysfunction and inflammation, independent of glucose lowering, and may represent a novel strategy for the treatment of age-related diseases.

Highlighted technique: In this study, a matrigel transplantation model was used to evaluate the senolytic effects of the SGLT2 inhibitor canagliflozin. Senescent cells were transplanted subcutaneously into mice together with matrigel and the reduction of these cells was assessed after drug treatment. The results showed that canagliflozin enhanced the immune-mediated clearance of senescent cells.

 Related technique  Cellular Senescence Detection (as used in this study),  Glucose Uptake Assay

The efficacy of chemotherapy is limited by intratumoral senescent cells expressing PD-L2 (Nature Cancer, 2024)
Chemotherapy-induced senescent cells upregulate PD-L2, helping them to evade immune clearance and persist in tumours. Loss of PD-L2 leads to their elimination, reduced CXCL1 and CXCL2 expression and limited immunosuppression. Anti-PD-L2 therapy with chemotherapy improves tumour regression and may offer a novel therapeutic strategy.

Highlighted technique: To investigate the role of PD-L2 in the persistence of senescent tumour cells, the authors used a chemotherapy-treated mouse tumour model and assessed senescent cells by p21 immunostaining and SA-β-gal staining.

 Related technique  Cellular Senescence Detection

Senescent-like microglia limit remyelination through the senescence associated secretory phenotype (Nature Communications, 2024)
In aged mice, the regenerative capacity of myelin in neuronal cells is significantly impaired, largely due to the accumulation of cellular senescence and increased expression of CCL11. These findings suggest a potential therapeutic target for age-related decline and multiple sclerosis.

Highlighted technique: In this study, to investigate the relationship between remyelination capacity and senescent cells, the researchers used INK-ATTAC mice, in which administration of the compound AP20187 selectively induces apoptosis in p16-positive senescent cells, allowing evaluation of the effects of senescent cell clearance in vivo.

 Related technique  Apoptosis Plate Assay