Bcl-2 / Bcl-xL survival network (SCAPs): senescence mechanism

Definition

Category: Survival / anti-apoptotic node

Also known as: SCAPs, Bcl-2 family, Bcl-xL, senescent-cell anti-apoptotic pathways

Senescent cells up-regulate anti-apoptotic 'senescent-cell anti-apoptotic pathways' (SCAPs), prominently the Bcl-2 family (Bcl-2, Bcl-xL, Bcl-w), to resist their own pro-apoptotic environment. Drugs that inhibit these proteins (navitoclax; components of the dasatinib+quercetin combination) can transiently disable the defence and trigger apoptosis selectively in senescent cells.

Key points

Navitoclax (ABT-263) is a Bcl-2/Bcl-xL inhibitor and a prototypical targeted senolytic in animal models.
On-target Bcl-xL inhibition causes thrombocytopenia (platelet loss), a key reason navitoclax has not advanced as a systemic human senolytic.
The 'transient disable, hit-and-run' concept underlies why intermittent dosing is used in senolytic trials.

Related interventions

Sourcing

Zhu et al. 2015/2016 (SCAP identification, navitoclax); standard senolytic reviews.

Reference synthesis (tier 4); verification: review_level_2026-07-12.