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衰老和衰老细胞溶解功能测定

senescence and senolytic functional assays.

作者信息

Ryan Patrick, Lee Jungwoo

机构信息

Molecular & Cellular Biology Graduate Program, University of Massachusetts, Amherst, Massachusetts, 01003, USA.

Department of Chemical Engineering, University of Massachusetts, Amherst, Massachusetts, 01003, USA.

出版信息

Biomater Sci. 2025 Jun 25;13(13):3509-3531. doi: 10.1039/d4bm01684j.

Abstract

A detailed understanding of aging biology and the development of anti-aging therapeutic strategies remain imperative yet inherently challenging due to the protracted nature of aging. Cellular senescence arises naturally through replicative exhaustion and is accelerated by clinical treatments or environmental stressors. The accumulation of senescent cells-defined by a loss of mitogenic potential, resistance to apoptosis, and acquisition of a pro-inflammatory secretory phenotype-has been implicated as a key driver of chronic disease, tissue degeneration, and organismal aging. Recent studies have highlighted the therapeutic promise of senolytic drugs, which selectively eliminate senescent cells. Compelling results from preclinical animal studies and ongoing clinical trials underscore this potential. However, the clinical translation of senolytics requires further pharmacological validation to refine selectivity, minimize toxicity, and determine optimal dosing. Equally important is the evaluation of senolytics' potential to restore tissue structure and function by reducing the senescent cell burden. In vitro tissue culture models offer a powerful platform to advance these efforts. This review summarizes the current landscape of systems used for inducing cellular senescence-referred to as "senescence assays"-and for screening senolytic drugs-referred to as "senolytic assays". We conclude by discussing key challenges to improving mechanistic insight, predictive accuracy, and clinical relevance in senolytic drug development, as well as emerging applications of senolytic therapies.

摘要

由于衰老过程的长期性,深入了解衰老生物学以及开发抗衰老治疗策略仍然至关重要,但本质上具有挑战性。细胞衰老通过复制性耗竭自然产生,并因临床治疗或环境应激因素而加速。衰老细胞的积累——其定义为有丝分裂潜能丧失、对凋亡的抵抗以及获得促炎分泌表型——被认为是慢性疾病、组织退化和机体衰老的关键驱动因素。最近的研究突出了衰老细胞溶解药物的治疗前景,这类药物能选择性地清除衰老细胞。临床前动物研究和正在进行的临床试验所取得的令人信服的结果强调了这种潜力。然而,衰老细胞溶解药物的临床转化需要进一步的药理学验证,以优化选择性、将毒性降至最低并确定最佳剂量。同样重要的是评估衰老细胞溶解药物通过减轻衰老细胞负担来恢复组织结构和功能的潜力。体外组织培养模型为推进这些工作提供了一个强大的平台。本综述总结了目前用于诱导细胞衰老的系统(称为“衰老检测”)以及用于筛选衰老细胞溶解药物的系统(称为“衰老细胞溶解检测”)的现状。我们通过讨论在衰老细胞溶解药物开发中提高机制洞察力、预测准确性和临床相关性的关键挑战以及衰老细胞溶解疗法的新兴应用来得出结论。

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