Senolytic intervention improves cognition, metabolism, and adiposity in female APP^NL^-F/NL-F mice.

ABSTRACT: Senescent cells accumulate throughout the body and brain contributing to unhealthy aging and Alzheimer's disease (AD). The APP^NL-F/NL-F amyloidogenic AD mouse model exhibits increased markers of senescent cells and the senescence-associated secretory phenotype (SASP) in visceral white adipose tissue and the hippocampus before plaque accumulation and cognitive decline. We hypothesized that senolytic intervention would alleviate cellular senescence thereby improving spatial memory in APP^NL-F/NL-F mice. Thus, 4-month-old male and female APP^NL-F/NL-F mice were treated monthly with vehicle, 5 mg/kg dasatinib + 50 mg/kg quercetin, or 100 mg/kg fisetin. Blood glucose levels, energy metabolism, spatial memory, amyloid burden, and senescent cell markers were assayed

SUBMITTER: Fang Y 

PROVIDER: S-EPMC11872876 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature