Analysis of the senescence-associated cell surfaceome reveals potential senotherapeutic targets.

IF 8 1区 医学 Q1 CELL BIOLOGY
Aging Cell Pub Date : 2024-09-03 DOI:10.1111/acel.14312
Yushuang Deng, Ting Liu, Enzo Scifo, Tao Li, Kan Xie, Bernd Taschler, Sarah Morsy, Kristina Schaaf, Armin Ehninger, Daniele Bano, Dan Ehninger
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Abstract

The accumulation of senescent cells is thought to play a crucial role in aging-associated physiological decline and the pathogenesis of various age-related pathologies. Targeting senescence-associated cell surface molecules through immunotherapy emerges as a promising avenue for the selective removal of these cells. Despite its potential, a thorough characterization of senescence-specific surface proteins remains to be achieved. Our study addresses this gap by conducting an extensive analysis of the cell surface proteome, or "surfaceome", in senescent cells, spanning various senescence induction regimes and encompassing both murine and human cell types. Utilizing quantitative mass spectrometry, we investigated enriched cell surface proteins across eight distinct models of senescence. Our results uncover significant changes in surfaceome expression profiles during senescence, highlighting extensive modifications in cell mechanics and extracellular matrix remodeling. Our research also reveals substantive heterogeneity of senescence, predominantly influenced by cell type and senescence inducer. A key discovery of our study is the identification of four unique cell surface proteins with extracellular epitopes. These proteins are expressed in senescent cells, absent or present at low levels in their proliferating counterparts, and notably upregulated in tissues from aged mice and an Alzheimer's disease mouse model. These proteins stand out as promising candidates for senotherapeutic targeting, offering potential pathways for the detection and strategic targeting of senescent cell populations in aging and age-related diseases.

Abstract Image

衰老相关细胞表面组分析揭示了潜在的衰老治疗靶点。
衰老细胞的积累被认为在与衰老相关的生理机能衰退和各种与年龄相关的病症的发病机制中起着至关重要的作用。通过免疫疗法靶向衰老相关的细胞表面分子是选择性清除这些细胞的一个很有前景的途径。尽管具有潜力,但衰老特异性表面蛋白的彻底表征仍有待实现。我们的研究针对这一空白,对衰老细胞的细胞表面蛋白质组(或称 "表面组")进行了广泛的分析,分析跨越了各种衰老诱导机制,涵盖了小鼠和人类细胞类型。利用定量质谱法,我们研究了八种不同衰老模型中富集的细胞表面蛋白。我们的研究结果揭示了衰老过程中表面组表达谱的重大变化,凸显了细胞力学和细胞外基质重塑的广泛改变。我们的研究还揭示了衰老的实质性异质性,主要受细胞类型和衰老诱导剂的影响。我们研究的一个关键发现是确定了四种具有胞外表位的独特细胞表面蛋白。这些蛋白在衰老细胞中表达,在增殖细胞中不表达或表达量很低,而且在衰老小鼠和阿尔茨海默病小鼠模型的组织中明显上调。这些蛋白有望成为衰老治疗靶点的候选蛋白,为检测衰老和老年相关疾病中的衰老细胞群并将其作为战略靶点提供了潜在途径。
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来源期刊
Aging Cell
Aging Cell Biochemistry, Genetics and Molecular Biology-Cell Biology
自引率
2.60%
发文量
212
期刊介绍: Aging Cell is an Open Access journal that focuses on the core aspects of the biology of aging, encompassing the entire spectrum of geroscience. The journal's content is dedicated to publishing research that uncovers the mechanisms behind the aging process and explores the connections between aging and various age-related diseases. This journal aims to provide a comprehensive understanding of the biological underpinnings of aging and its implications for human health. The journal is widely recognized and its content is abstracted and indexed by numerous databases and services, which facilitates its accessibility and impact in the scientific community. These include: Academic Search (EBSCO Publishing) Academic Search Alumni Edition (EBSCO Publishing) Academic Search Premier (EBSCO Publishing) Biological Science Database (ProQuest) CAS: Chemical Abstracts Service (ACS) Embase (Elsevier) InfoTrac (GALE Cengage) Ingenta Select ISI Alerting Services Journal Citation Reports/Science Edition (Clarivate Analytics) MEDLINE/PubMed (NLM) Natural Science Collection (ProQuest) PubMed Dietary Supplement Subset (NLM) Science Citation Index Expanded (Clarivate Analytics) SciTech Premium Collection (ProQuest) Web of Science (Clarivate Analytics) Being indexed in these databases ensures that the research published in Aging Cell is discoverable by researchers, clinicians, and other professionals interested in the field of aging and its associated health issues. This broad coverage helps to disseminate the journal's findings and contributes to the advancement of knowledge in geroscience.
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