p53-Induced Senescence Links Lysosomal and Autophagy Activation [Feb. 24, 2026] DOJINDO LABORATORIES

p53 activation contributes to tumor suppression in cancer and can induce cellular senescence depending on context. This article highlights recent findings on p53-driven senescence and its relationship to lysosome and autophagy pathways. Recent studies showed that, in senescent cells, p53 promotes autophagy- and lysosome-dependent lipid recycling, increasing phosphoethanolamine supply to meet phospholipid demand from cellular hypertrophy and organelle remodeling. In a lung cancer model, p53 reactivation induced a TSC2-mTORC1-TFEB cascade that upregulated lysosome and autophagy programs, leading to autophagy-dependent senescence and tumor regression through macrophage-mediated clearance of senescent cells. Together, these findings advance our understanding of p53-driven senescence and indicate that lysosome and autophagy pathways contribute to this process.

p53 increases phospholipid headgroup scavenging in senescence (Nature Cell Biology, 2026)
Summary: p53 is a stress-responsive tumor suppressor that can induce cellular senescence, in which hypertrophy and membrane/organelle remodeling increase phospholipid demand. This study shows that in senescent cells p53 promotes autophagy- and lysosome-dependent lipid headgroup scavenging, increasing phosphoethanolamine (PEtn) supply to support phosphatidylethanolamine (PE) synthesis and creating dependence on the PE biosynthetic pathway.

Highlighted technique: SA-βGal , a senescence marker based on lysosome-derived β-galactosidase activity, was used to confirm and quantify senescence under p53 ON/OFF and PE synthesis–inhibiting conditions. p53 was controlled by Nutlin-3a–mediated activation or dox-based p53 ON/OFF regulation, and the senescent fraction was quantified by counting the percentage of SA-βGal–positive cells.

p53 Drives Lung Cancer Regression through a TSC2/TFEB-dependent Senescence Program (Cancer Discovery, 2026)
Summary: In a lung cancer model, reactivation of p53 induced a TSC2–mTORC1–TFEB cascade that upregulated lysosome/autophagy programs, and the resulting increase in autophagy was required for establishing cellular senescence. Senescent cancer cells then produced SASP-like signals that recruited macrophages into tumors to promote senescent-cell clearance, thereby driving tumor regression.

Highlighted technique: The authors tested whether p53 reactivation truly increases autophagy activity in lung cancer cells by monitoring LC3-II, an autophagosome-associated marker, and the lysosomal marker LAMP1. After confirming that p53 elevated LC3-II and LAMP1, they added bafilomycin and observed further LC3-II accumulation, supporting active autophagic flux rather than impaired degradation under p53 reactivation.

Senescence, Autophagy and Lysosome Indicators (click to open/close)

Target	Kit & Probes
Senescence-associated β-gal detection	SPiDER-βGal for live-cell imaging or flow cytometry / microplate reader / tissue samples Blue cellular senescence detection dye for fixed cells, SPiDER Blue
First-time autophagy research	Autophagic Flux Assay Kit
Lysosomal Function Analysis Kit	Lysosomal Acidic pH Detection Kit -Green/Red and Green/Deep Red
High Specific Lysosommal Mass Detection	LysoPrime Green / Deep Red
Lysosomal Acidic pH Detection	pHLys Red
Mitophagy detection	Mitophagy Detection Kit
Endocytosis Detection	ECGreen-Endocytosis Detection

Application Note (click to open/close)
> 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