数据日期 2026-10-29 · 生成时间 2026-10-29 06:03
研究问题
The senomorphic field has accumulated a substantial body of preclinical evidence, yet the translation of this evidence into clinical benefit remains largely unrealized.
方法
We argue in this review that the central obstacle is not a lack of mechanistic insight, but rather the absence of tissue-selective delivery strategies, validated senescence biomarkers, and compounds with well-defined dose-response relationships in aged organisms.
核心结论
Early-phase SASP is characterized by secretion of transforming growth factor-β (TGF-β), chemokines, and pro-inflammatory cytokines.；When TGF-β signaling is activated, through either autocrine or paracrine mechanisms, it helps establish and sustain the senescent phenotype (Lagoumtzi and Chondrogianni, 2021; Roberts et al., 1981; Rapisarda et al., 2017).；If senescent cells are not cleared promptly and instead accumulate, this early SASP signature persists and transitions to a late-phase program, driven largely by sustained upregulation of the transcriptional regulators nuclear factor kappa B (NF-κB) and CCAAT/enhancer-binding protein β (C/EBPβ) (Lagoumtzi and Chondrogianni, 2021; Chien et al., 2011; Orjalo et al., 2009; Hoare et al., 2016). ‖ 结论：Whether senomorphics will become a cornerstone of anti-aging medicine or remain a mechanistically fascinating but practically limited set of tools will ultimately depend on how effectively these scientific and clinical challenges are met.
局限
The former group arguably warrants accelerated investigation precisely because the pharmacological unknowns are fewer.；Future research should address several specific priorities: 1) single-cell SASP profiling to resolve the cellular heterogeneity of senescence and identify subpopulations most relevant to specific diseases; 2) development of targeted delivery systems that can concentrate senomorphic activity in pathologically senescent tissue while limiting systemic exposure; 3) systematic evaluation of combinatorial strategies that integrate senomorphics with senolytics or immunomodulatory approaches; and 4) mechanistic clarification of the context-specific beneficial functions of the SASP…
对本项目的价值
★★★☆☆ 细胞衰老清除/重编程是项目干预管线的核心支柱之一。命中核心 细胞衰老。
全文来源
PMC JATS 全文（正文 57,206 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：Silencing without clearing: pharmacological modulation of the SASP in aging and disease.
- 期刊与标识：Front Pharmacol · PMID 42935667 · DOI 10.3389/fphar.2026.1911529**
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