时间标签：数据日期 2026-10-31 · 生成时间 2026-11-01 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/10/28–2026/10/31 ｜ 情报发生日期 2026-10-31
研究问题
Persistent senescent-cell accumulation may arise, however, when cell production exceeds local clearance or when immune surveillance becomes ineffective ().；Adaptive immune cells, natural killer cells, and macrophages can participate in senescent-cell recognition and clearance in the liver, although direct evidence that this process fails in human MASLD remains limited ().；It also remains unclear which senescent hepatocyte states are preferentially retained, which ligand–receptor interactions determine immune recognition or escape, and when a potentially adaptive senescent response becomes persistently pathogenic.
方法
CD4-positive T cells acted with recruited monocytes and monocyte-derived macrophages to remove senescent hepatocytes, whereas resident Kupffer cells were not the principal effector population ().；Importantly, the recruited monocyte-derived macrophages described in this model should be distinguished from resident Kupffer cells, because these populations differ in origin, localization, and functional responses to hepatic injury.；Experimental fatty liver is accompanied by remodeling of resident Kupffer-cell populations and the emergence of recruited lipid-associated macrophages with distinct transcriptional programs ().
核心结论
Metabolically stressed hepatocytes may undergo reversible adaptation, cell death, or other stress responses; senescence should therefore be viewed as one potential cell fate that may complement, rather than replace, these established mechanisms of MASLD progression.；Human studies have reported increased hepatocyte p21 expression, telomere-associated DNA damage, and nuclear enlargement in association with more advanced fibrosis, while experimental studies have identified increased senescence-associated beta-galactosidase activity, cell-cycle inhibitor expression, and senescent-hepatocyte gene signatures (–).；Together, these observations support a biological association between hepatocyte senescence and MASLD severity, although they do not establish senescence as a uniform or dominant driver of disease progression. ‖ 结论：Taken together, the key issue is not simply whether senescent hepatocytes accumulate, but when a transient stress response becomes a persistent state that escapes effective clearance and drives maladaptive tissue remodeling.
局限
This heterogeneity, together with the lack of a single specific senescence marker, remains an important limitation when interpreting both experimental and human studies.；Future studies should therefore address the specific barriers identified in this Review by combining multiplex spatial profiling of human liver tissue with multi-marker senescence identification, longitudinal or lineage-tracing approaches, and functional assays of immune recognition and killing.
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。
全文来源
PMC JATS 全文（正文 33,148 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：Impaired immune surveillance of senescent hepatocytes in MASLD: SASP signaling and fibrogenic progression.
- 期刊与标识：Front Immunol · PMID 42953355 · DOI 10.3389/fimmu.2026.1982821
A 级证据分级：A 级（同行评议人体研究）
本文属人体研究证据，但需注意：观察性或小样本干预的结论不等于已证实临床获益；效应量与长期安全性仍需更大规模、更长随访的试验验证。
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