时间标签：数据日期 2026-11-03 · 生成时间 2026-11-03 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/10/31 – 2026/11/03 ｜ 情报发生日期 2026-11-03
研究问题
23 Collectively, these observations support testing whether pharmacological AEP inhibition can ameliorate aging-related phenotypes.；We therefore evaluated whether the optimized AEP inhibitor #11a, which displays good oral bioavailability and favorable in vivo pharmacokinetic (PK) profiles, could elicit longevity effects in naturally aging C57BL/6 wild-type mice.；Thereafter, we tested the effects of #11a treatment on age-dependent phenotypes utilizing the mixed model ( Figures 1 E and 1F). #11a significantly decreased the severity of multiple age-dependent phenotypes in females, including mouse grimace, body condition, forelimb grip strength, and hearing loss.
方法
11 , 24 , 25 Mice were fed a standard chow diet or a diet supplemented with #11a at 0.056 g/kg feed (equivalent to ∼7.5 mg/kg/day) starting at approximately 18 months of age, and lifespan and health span analyses were initiated concurrently.；Starting at 18 months of age, we conducted repeated assessments every 4 weeks, generating 14 to 15 datasets per group.；Because we measured the same mice over time, we used a mixed model that treated each mouse as a random effect and treatment/time as fixed effects.
核心结论
20 , 21 Most recently, we showed that AEP is augmented in atherosclerosis plaques obtained from patients and proteolytically cuts apolipoprotein A1 (APOA1), impairing cholesterol efflux and high-density lipoprotein (HDL) formation, thereby facilitating atherosclerotic pathologies.；23 Collectively, these observations support testing whether pharmacological AEP inhibition can ameliorate aging-related phenotypes.；Thereafter, we tested the effects of #11a treatment on age-dependent phenotypes utilizing the mixed model ( Figures 1 E and 1F). #11a significantly decreased the severity of multiple age-dependent phenotypes in females, including mouse grimace, body condition, forelimb grip strength, and hearing loss.
局限
As an enzyme, AEP specifically cleaves its substrates after asparagine residues and is primarily localized to the endo-lysosomal system 3 ; however, under pathophysiological conditions, AEP is also localized in the cytoplasm or in the nucleus.；In the open-field test, #11a-treated mice showed altered exploratory behavior, including increased total distance moved, increased center exploration, and reduced immobility time, although these findings should be interpreted cautiously because the current dataset does not fully distinguish anxiety-related behavior from general locomotor changes ( Figures 2 C and 2E).
对本项目的价值
中高价值：属「衰老细胞清除 / SASP 轴」方向；其他衰老相关栏目可用作本项目文献库与综述素材。 ｜ 价值分 3.0/5（★★★☆☆）
全文来源
PubMed PMC JATS（正文 71,526 字符，题名指纹 1.00，已过 DOI 逐字 + 题名指纹 + 正文长度三重归属校验）
原文题录
- 中文题名：抑制天冬酰胺内肽酶延长寿命并改善衰老期健康跨度
- 英文标题：Inhibition of asparagine endopeptidase extends the lifespan and improves health span during aging.
- 期刊与标识：iScience · PMID 42964811 · DOI 10.1016/j.isci.2026.117990 · PMC PMC13720683 · EDAT 2026-10-31