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
The aim of this study was to analyze autophagy flux in an aging cell system based on primary dermal fibroblasts from different healthy individuals with an age range that reflects aging (20–96 years).
方法
The following human dermal fibroblast cultures were utilized: Skin primary fibroblasts from apparently healthy men donors aged 20 years (GM03440), 38 years (AG08469), 74 years (AG06290), and 96 years (AG04059) were obtained from the Coriell Institute for Medical Research (Camden, NJ).；Cultures were then subjected to immunofluorescence (IF) and Western blot (WB) analyses.；All experiments used donor-matched cell cultures, restricted to passages 4–10 to maintain biological comparability across cohorts.；For double staining, cells were subjected to an overnight incubation at 4 °C with the appropriate primary antibody.
核心结论
The accumulation of TFEB increased markedly in the nucleus of all the different age-donor fibroblasts when grown in starvation conditions, with fibroblasts from a 96-year-old donor exhibiting the highest nuclear fluorescence ().；On the other hand, we found that the immunoreactive band corresponding to phospho-TFEB (p-TFEB) virtually disappeared in all fibroblast lysates from different donor ages when cultured under starvation conditions ().；Instead, a series of lower-migrating bands were observed. ‖ 结论：However, these findings indicate the preservation of selective downstream responses rather than fully intact overall TFEB activity.
局限
This aging cell model is well-established and widely employed for studying the cellular and molecular changes associated with aging (; ; ; ; ; ; .) Autophagy exhibits a close association with the aging process, yet despite the extensive research conducted on this process, there is a lack of studies, specifically on autophagic flux, which is required to understand its various stages.；This limitation is of relevance when evaluating autophagy flux, a multi-step and tightly regulated pathway, which may be influenced by the metabolic or genetic baseline of each individual.；Consequently, future studies incorporating biological replicates from additional donors within the same age cohorts will be n
对本项目的价值
★★☆☆☆ 营养感知与自噬轴决定「干预窗口 + 剂量方案」，是组合疗法的时间锚。
全文来源
PMC JATS 全文（正文 38,747 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：Impaired autophagy and lysosome function in human fibroblast aging.
- 期刊与标识：Front Aging · PMID 42953013 · DOI 10.3389/fragi.2026.1971981
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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