Pharmacologic activation of delta133p53α reduces cellular senescence in progeria patients-derived cells
Celastrol and ADZ1981 upregulate endogenous Δ133p53α and, reproducing the effects of its vector-driven expression, inhibit cellular senescence and IL-6 secretion in HGPS-derived fibroblasts. Their progerin-independent action suggests that they may synergize with currently available progerin-targeting therapies. This study also warrants further investigation of these compounds for potential applications in other diseases and conditions in which Δ133p53α-regulated senescence plays a role.
Authors
- Patricia Dranchak (ORCID: https://orcid.org/0000-0002-1349-4885)
- Curtis C. Harris (ORCID: https://orcid.org/0000-0001-5268-0181)
- Natalia von Muhlinen (ORCID: https://orcid.org/0000-0003-4331-3114)
- Sebastien M. Joruiz (ORCID: https://orcid.org/0000-0002-5613-2665)
- James Inglese (ORCID: https://orcid.org/0000-0002-7332-5717)
- Izumi Horikawa (ORCID: https://orcid.org/0000-0002-2893-5014)
- Delphine Lissa
Institutions
- National Institutes of Health (US)
- National Human Genome Research Institute (US)
- National Cancer Institute (US)
- National Center for Advancing Translational Sciences (US)
- Center for Cancer Research (US)
Publication Details
- Journal
- Aging Pathobiology and Therapeutics
- Published
- 2025-09-25
- DOI
- https://doi.org/10.31491/apt.2025.09.185
- Citations
- 1
- Primary Topic
- Nuclear Structure and Function
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- National Institutes of Health