Uncovering Hidden Mechanisms of Cellular Senescence [Sep. 2, 2025] DOJINDO LABORATORIES

New Insights Reveal How Senescence Spreads and Enlarged Cells Are Sustained
Aging is increasingly seen as a key factor behind many diseases, driving the search for ways to slow or prevent it. Recent work has shown that the protein HMGB1 can transmit senescence signals between cells and even to distant tissues, and that blocking this process supports tissue repair. Another study identified AP2A1 as a factor that keeps senescent cells enlarged, with its inhibition reversing aging traits. Together, these findings point to new possibilities for targeting the fundamental mechanisms of aging to improve health and longevity.

Related technique

Propagation of senescent phenotypes by extracellular HMGB1 is dependent on its redox state (Metabolism, 2025)
Summary: This study identifies redox-sensitive HMGB1 (ReHMGB1) as a novel driver of cellular senescence that spreads from one cell to its neighbors and through the bloodstream to distant organs. Blocking extracellular HMGB1 was shown to reduce systemic senescence and improve tissue regeneration, suggesting its potential as a therapeutic target for aging-related diseases.

Highlighted technique: The study evaluated cellular senescence using SA β gal staining to identify senescent cells and EdU incorporation to assess proliferative arrest. Expression levels of p16 and p21 were also measured as molecular markers of cell cycle inhibition.

AP2A1 modulates cell states between senescence and rejuvenation (Cellular Signalling, 2025)
Summary: Senescent cells are markedly larger than young cells, a feature that drives further aging and disease, yet the molecular basis of this enlarged architecture has remained unclear. This study reveals that AP2A1 reinforces integrin β1–mediated anchorage to maintain cell size, and its inhibition reverses senescence phenotypes, highlighting AP2A1 as a potential therapeutic target for aging-related conditions.

Highlighted technique: The study combined SA β gal staining with quantitative analysis of cell size to directly link senescence associated β galactosidase activity to the pronounced hypertrophy of senescent cells. This morphological and biochemical readout was then applied to assess the effects of AP2A1 knockdown on SA β gal positivity and cellular enlargement.

Application Note > Senescent Cells Lose Mitochondrial Activity

NAD(+) levels decline during the aging process, causing defects in nuclear and mitochondrial functions and resulting in many age-associated pathologies*. Here, we try to redemonstrate this phenomenon in the doxorubicin (DOX)-induced cellular senescence model with a comprehensive analysis of our products.

*S. Imai, et al., Trends Cell Biol, 2014, 24, 464-471

Products in Use
① DNA Damage Detection Kit - γH2AX
② Cellular Senescence Detection Kit - SPiDER-βGal
③ NAD/NADH Assay Kit-WST
④ JC-1 MitoMP Detection Kit
⑤ Glycolysis/OXPHOS Assay Kit、Lactate Assay Kit-WST

Related Techniques

Target	Kit & Probes
Cellular senescence detection	SPiDER-βGal for live-cell imaging or flow cytometry / microplate reader / tissue samples Blue cellular senescence detection dye for fixed cells, SPiDER Blue
Lysosomal function	Lysosomal Acidic pH Detection Kit -Green/Red and Green/Deep Red
First-time autophagy research	Autophagic Flux Assay Kit
Mitophagy detection	Mitophagy Detection Kit
Mitochondrial membrane potential detection	JC-1 MitoMP Detection Kit, MT-1 MitoMP Detection Kit
Endocytosis Detection	ECGreen-Endocytosis Detection
ATP Measurement	ATP Assay Kit-Luminescence
Apoptosis detection in multiple samples	Annexin V Apoptosis Plate Assay Kit
Cell proliferation/ cytotoxicity assay	Cell Counting Kit-8 and Cytotoxicity LDH Assay Kit-WST