The work, led by Yuanzhu Pu and Can Su, with corresponding author Haifeng Chen, builds on a long history of pharmacological interest in E. breviscapus. The herb, known in Chinese medicine as Dengzhan Xixin, has documented antioxidant, anti-apoptotic, and anti-inflammatory properties, and its principal constituents, including caffeoylquinic acids and the flavonoid scutellarin, have been examined for effects ranging from improved insulin sensitivity to vascular protection. What remained poorly understood, the authors note, was whether the plant could meaningfully counter cellular senescence itself, the progressive decline in cell function that underlies tissue deterioration, and if so, through which molecular machinery.

To answer that question, the researchers deployed a classic one-two punch of aging research models. The first was Caenorhabditis elegans, the transparent nematode worm that has served for decades as the workhorse of longevity genetics, allowing researchers to test lifespan effects with unprecedented genetic precision. The second was the senescence-accelerated mouse prone 8 strain, or SAMP8, a murine line that exhibits premature and exaggerated aging phenotypes, making it a useful bridge between short-lived invertebrates and mammalian physiology. Using both systems in parallel allowed the team to ask not only whether the herb works, but whether its mechanism is conserved across species separated by hundreds of millions of years of evolution.

In the worms, the results were striking. EBHM treatment prolonged average lifespan by a maximum of 18.68 percent, a substantial figure in a field where even single-digit extensions are considered noteworthy. Beyond mere survival, the treated nematodes showed significantly enhanced resistance to stress and improved motor function, indicating that the herb extended healthspan, the biologically active portion of life, rather than simply stretching out a period of frailty. The researchers also measured reduced levels of malondialdehyde, a marker of lipid damage caused by reactive oxygen species, alongside increased activity of the cell’s primary antioxidant enzymes: superoxide dismutase, glutathione peroxidase, and catalase.

The genetic dissection is where the study becomes particularly compelling. When the team repeated the lifespan experiments in mutant worms lacking functional copies of key longevity genes, the effect of the herb vanished entirely. Mutants in aak-2, the worm homolog of the metabolic sensor AMPK; sir-2.1, the nematode version of the sirtuin SIRT1; daf-16, the worm’s FOXO transcription factor; and cep-1, its p53 homolog, all failed to benefit from EBHM treatment. This pattern of epistasis, in which a compound’s effect disappears when a specific gene is disabled, is strong evidence that the herb acts through that pathway rather than through some unrelated mechanism. In other words, the plant’s longevity benefit appears to require the same genetic circuitry that caloric restriction and other proven lifespan interventions engage.

The molecular readouts filled in the picture. EBHM treatment increased the ratio of phosphorylated to total AMPK, indicating activation of this cellular energy sensor, and elevated levels of SIR-2.1 protein, the deacetylase that cooperates with AMPK in longevity regulation. The researchers used fluorescent reporter strains to watch the pathway in action: DAF-16::GFP, a tagged FOXO protein, migrated into the nucleus, where it can switch on antioxidant genes, and SOD-3::GFP, a reporter for a superoxide-dismutating enzyme under FOXO control, lit up in treated worms. These effects were dependent on DAF-16, confirming that the herb’s antioxidant boost flows through FOXO-mediated transcription rather than a direct chemical scavenging effect alone.

The team also probed the apoptosis arm of the mechanism. In the worms, EBHM downregulated the messenger RNA levels of cep-1 and ced-3, the pro-apoptotic genes corresponding to mammalian p53 and caspase-3, while upregulating ced-9, the homolog of the anti-apoptotic gene Bcl-2. This shift suggests the herb tilts the balance away from programmed cell death, a process that becomes dysregulated in aged tissues and contributes to functional decline. The finding dovetails with the broader understanding that SIRT1, when activated, deacetylates and thereby modulates p53, damping down excessive apoptotic signaling while preserving the tumor-suppressive functions that make p53 indispensable.

The mammalian experiments translated these findings into tissue-level outcomes. In SAMP8 mice treated with EBHM, the liver and kidney, organs that accumulate senescent cells and fibrotic damage with age, showed clear improvement. The number of cells staining positive for senescence-associated beta-galactosidase, a classic marker of cellular senescence, decreased, as did collagen deposition and expression of alpha-smooth muscle actin, both indicators of fibrosis. At the molecular level, the treated mice displayed elevated p-AMPK/AMPK ratios and SIRT1 expression, along with reduced levels of acetylated FOXO3a, p53, acetylated p53, p16, and p21, the latter two being canonical senescence-effectors that arrest the cell cycle. Malondialdehyde levels fell while antioxidant enzyme activities rose, the proportion of apoptotic cells diminished, the pro-apoptotic proteins Bax and caspase-3 were downregulated, and Bcl-2 was upregulated.

Taken together, the data sketch a coherent mechanistic model. EBHM activates AMPK, which in turn boosts SIRT1. Active SIRT1 deacetylates FOXO3a, freeing the transcription factor to enter the nucleus and upregulate antioxidant defense genes, which lowers oxidative stress and the lipid damage it causes. Simultaneously, SIRT1-mediated deacetylation of p53 restrains p53-driven apoptosis, while the downstream senescence markers p16 and p21 recede. The result, in both worm and mouse, is less oxidative damage, fewer senescent cells, less fibrotic scarring, and better-preserved tissue function. The authors conclude that the herb alleviates senescence through this AMPK-SIRT1 pathway, enhancing FOXO3a-dependent antioxidant defenses and modulating p53-mediated apoptosis.

The study carries obvious appeal in a field hungry for interventions that engage conserved longevity pathways, and it fits within a growing body of work on plant polyphenols as activators of sirtuin signaling, a concept sometimes framed as xenohormesis, the idea that plants under stress produce compounds that can confer stress resistance on the animals that consume them. Yet important caveats remain. The findings derive from nematodes and a mouse strain prone to accelerated aging, and the effective doses, bioavailability, and long-term safety of EBHM preparations in humans have not been established. The herb is already used clinically in China, primarily in formulations for cardiovascular and cerebrovascular conditions, which offers a measure of human safety data, but anti-aging applications would demand rigorous clinical trials. The datasets from the current study are available from the corresponding author upon reasonable request, and the work was funded by Yunnan Provincial science and technology programs. For now, the study stands as a technically thorough demonstration that a traditional medicinal plant can engage the AMPK-SIRT1-FOXO3a/p53 axis across species, a result that should energize the search for standardized, mechanism-validated anti-aging compounds from the pharmacopoeia of traditional medicine.

Subject of Research: Anti-senescence effects and AMPK-SIRT1 mechanism of the medicinal herb Erigeron breviscapus in C. elegans and SAMP8 mice

Article Title: Erigeron breviscapus alleviates senescence via AMPK-SIRT1 signaling by modulating FOXO3a-mediated antioxidant defense and p53-dependent apoptosis

Article References: Pu, Y., Su, C., Wang, X., & Chen, H. (2026). Erigeron breviscapus alleviates senescence via AMPK-SIRT1 signaling by modulating FOXO3a-mediated antioxidant defense and p53-dependent apoptosis. Biogerontology, 27(5), Article 166. https://doi.org/10.1007/s10522-026-10511-3

Image Credits: AI Generated

DOI: 10.1007/s10522-026-10511-3

Keywords: Erigeron breviscapus, aging, cellular senescence, AMPK-SIRT1, FOXO3a, p53, apoptosis, antioxidant defense, Caenorhabditis elegans, SAMP8 mice, traditional Chinese medicine, lifespan extension