Rejuvenation by Therapeutic Elimination of Senescent Cells.
Krimpenfort. Paul P; Berns. Anton A
Key Findings
- FOXO4 binds p53 in senescent cells, keeping p53 from triggering cell death.
- An all‑D amino‑acid version of FOXO4 (FOXO4‑DRI) disrupts this binding, allowing p53 to induce apoptosis of senescent cells.
- Treating mice with FOXO4‑DRI reduced senescent cell burden and improved tissue function.
Practical Outcomes
- For biohackers, FOXO4‑DRI represents a promising new senolytic approach, but it is still at the pre‑clinical stage. No human dosing, safety, or delivery data are available yet, so it cannot be recommended for self‑administration. Keep an eye on future trials for possible protocols once safety and efficacy in people are established.
Summary
A new peptide called FOXO4‑DRI can make old, damaged cells (senescent cells) die by freeing the protein p53 to do its job. In mouse studies this cleared those bad cells and helped tissues work better, suggesting a possible way to fight aging‑related decline.
Abstract
In this issue of Cell, Baar et al. show how FOXO4 protects senescent cell viability by keeping p53 sequestered in nuclear bodies, preventing it from inducing apoptosis. Disrupting this interaction with an all-D amino acid peptide (FOXO4-DRI) restores p53's apoptotic role and ameliorates the consequences of senescence-associated loss of tissue homeostasis.
Study Information
pubmed
2017
2017-03-23T00:00:00.000Z
10.1016/j.cell.2017.03.014
18
9