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A new study shows that inhibiting the epigenetic enzyme p300 protects cells, neurons, and even brain organoids from stress-induced premature senescence.
The Discovery:
Researchers demonstrated that the p300 inhibitor CCS1477 reduced DNA damage, senescence markers, and inflammation in multiple human cell models. This highlights p300 as a promising drug target for age-related diseases, including neurodegenerative disorders.
The Science:
Senescence background: Stress-induced premature senescence (SIPS) arises from DNA damage and fuels aging and disease.
Patient cells: Lymphoblastoid cells with EP300 mutations were less sensitive to senescence, confirming p300’s role as a driver.
Chemical inhibition: In healthy donor cells, CCS1477 reduced DNA damage (γH2AX), and lowered p21, p53, CDKN1A, GLB1, IL6.
iNeurons: In human induced neurons, CCS1477 cut β-gal positivity and SASP gene expression, protecting against oxidative and genotoxic stress.
Brain organoids: In 3D neural tissue, p300 inhibition reversed senescence markers and restored gene programs linked to neuronal activity.
Transcriptomics: Treated organoids clustered closer to controls than stressed ones, confirming rescue at the molecular level.
Your Action:
p300 inhibitors like CCS1477 are still experimental. For now, reduce premature senescence by managing oxidative stress: avoid smoking, limit toxin exposure, and support DNA repair through sleep, balanced diet, and exercise.
Bottom Line:
Targeting p300 may open new therapeutic avenues to delay cellular senescence and combat neurodegenerative aging.
Source:
p300 inhibition delays premature cellular senescence. npj Aging. Di Fede E, Taci E, Castiglioni S, Rebellato S, Ancona S, Grazioli P, Parodi C, Colombo EA, Bernardelli C, Lesma E, Krantz ID, Corti S, Priori A, Fazio G, Gervasini C, Massa V, Lettieri A.
https://doi.org/10.1038/s41514-025-00251-y
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This newsletter is for informational purposes only and does not substitute professional medical advice. Always consult with a healthcare provider before making any changes to your health regimen.