A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues

Although cellular senescence drives multiple age-related co-morbidities
through the senescence-associated secretory phenotype (SASP), in vivo
senescent cell identification remains challenging. Here, we generated a
gene set (SenMayo) and validated its enrichment in bone biopsies from two
aged human cohorts. We further demonstrated reductions in SenMayo in bone
following genetic clearance of senescent cells in mice and in adipose
tissue from humans following pharmacological senescent cell clearance. We
next used SenMayo to identify senescent hematopoietic or mesenchymal cells
at the single cell level from human and murine bone marrow/bone scRNA-seq
data. Thus, SenMayo identifies senescent cells across tissues and species
with high fidelity. Using this senescence panel, we were able to
characterize senescent cells at the single-cell level and identify key
intercellular signaling pathways. SenMayo also represents a potentially
clinically applicable panel for monitoring senescent cell burden with
aging and other conditions as well as in studies of senolytic drugs.

尽管细胞衰老可通过衰老相关分泌表型（senescence-associated secretory phenotype，SASP）驱动多种年龄相关共病的发生，但体内衰老细胞的识别仍颇具挑战。本研究构建了基因集SenMayo，并在两个老年人类队列的骨活检样本中验证了该基因集的富集特性。本研究进一步证实，在小鼠体内通过遗传学手段清除衰老细胞后，其骨组织中SenMayo的表达水平显著下调；在人类受试者中，经药物性清除衰老细胞后，其脂肪组织内的SenMayo表达水平同样出现降低。随后，本研究利用SenMayo基因集，从人类与小鼠的骨髓/骨组织单细胞RNA测序（single-cell RNA sequencing，scRNA-seq）数据中，精准鉴定出造血细胞与间充质类衰老细胞。综上，SenMayo可在不同组织与物种间实现高保真的衰老细胞识别。借助该衰老特征基因集，本研究可在单细胞层面完成衰老细胞的表征，并鉴定出关键的细胞间信号通路。此外，SenMayo还具备潜在的临床应用价值，可用于监测衰老及其他疾病状态下的衰老细胞负荷，同时也可应用于衰老清除药物的相关研究。

搜集汇总

背景与挑战

背景概述

该数据集包含一个名为SenMayo的新基因集，用于在多种组织和物种中高保真地识别衰老细胞，并预测衰老相关信号通路。它基于原始基因计数数据，支持在单细胞水平分析衰老细胞，并具有监测衰老细胞负担和评估抗衰老药物的潜在临床应用价值。