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Updated: Jan 22, 2026
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Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes
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Proteolysis-targeting chimera (PROTAC): A promising senolytic strategy
Gang Fan1, Qingping Zhang2, Weiming Guo3
1Medical Research Center, Affiliated Nanshan Hospital of Shenzhen University, Shenzhen 518052, China; Pan-Vascular Research Group, Affiliated Nanshan Hospital of Shenzhen University, Shenzhen 518052, China.
Ageing Research Reviews
|January 20, 2026
Summary
Proteolysis-targeting chimeras (PROTACs) offer a novel senolytic strategy by degrading anti-apoptotic proteins in senescent cells. This approach targets "undruggable" proteins, advancing senolysis for age-related diseases.
Area of Science:
- Biochemistry
- Gerontology
- Pharmacology
Background:
- Senescent cells (SCs) accumulate with aging, driving age-related diseases.
- SCs evade apoptosis via upregulated senescent cell anti-apoptotic pathways (SCAPs).
- Selective elimination of SCs (senolysis) is a promising therapeutic strategy.
Purpose of the Study:
- To review PROTAC technology principles and advances.
- To focus on PROTACs as a senolytic strategy.
- To discuss challenges in advancing PROTAC senolytics for clinical use.
Main Methods:
- Review of scientific literature on PROTACs and senolysis.
- Analysis of PROTAC mechanisms targeting SCAP components.
- Comparative analysis of PROTAC classes targeting senescence regulators.
Main Results:
- PROTACs degrade target proteins by hijacking the ubiquitin-proteasome system.
- PROTACs can overcome limitations of conventional inhibitors for SCAP proteins.
- PROTACs offer a novel approach to clear senescent cells.
Conclusions:
- PROTACs represent a promising senolytic strategy for age-related diseases.
- Targeting SCAP proteins with PROTACs can effectively clear senescent cells.
- Addressing aging-specific challenges is crucial for clinical translation of PROTAC senolytics.
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