Elimination of senescent cells by mechanical cell competition

作者：Yuping Pan, Mattheus Xing Rong Foo, Vinod S/O Prabhakaran, Kashish Jain, Pakorn Kanchanawong, Oliver Dreesen, Yusuke Toyama · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2026 · DOI：10.64898/2026.05.18.725837 · 被引用次数：2 · 研究领域：Telomeres, Telomerase, and Senescence、Nuclear Structure and Function、Retinoids in leukemia and cellular processes

Abstract Cellular senescence, a hallmark of aging, leads to the accumulation of apoptosis-resistant cells that compromise tissue homeostasis. While senescent cells are known to influence neighboring cells through the senescence-associated secretory phenotype (SASP), the precise nature of the interactions between senescent and normal cells remains elusive. Here we show that progerin-induced senescent cells undergo apoptosis when co-cultured with normal cells. This elimination requires direct cell-cell contact and is mediated by the JNK and p38-MAPK pathways, leading to p53 upregulation and p21 downregulation in progerin-expressing cells. Furthermore, neighboring normal cells exert persistent mechanical compression on progerin-expressing cells prior to their elimination, consistent with mechanical cell competition. In contrast, p16-induced senescent cells resist elimination under the same co-culture conditions, maintaining high p21 levels. Our findings reveal a non-cell-autonomous mechanism for senescent cell clearance, providing new insights into the maintenance of tissue homeostasis during aging.