Cell enlargement modulated by GATA4 and YAP instructs the senescence-associated secretory phenotype

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 17, 2025

Dynamic changes in cell size are associated with development and pathological conditions, including aging. Although enlargement is a prominent morphological feature of cellular senescence, its functional implications unknown; moreover, how senescent cells maintain their state less understood. Here we show that an extensive remodeling actin cytoskeleton necessary for establishing senescence-associated pro-inflammatory secretory phenotype (SASP). This attributed to balancing act between the SASP regulator GATA4 mechanosensor YAP on expression Rho family GTPase RHOU. Genetic or pharmacological interventions reduce attenuate minimal effect senescence growth arrest. Mechanistically, couples nuclear localization NF-κB via Linker Nucleoskeleton Cytoskeleton (LINC) complex. RhoU protein accumulates mouse adipose tissue under senescence-inducing conditions. Furthermore, RHOU correlates during human Thus, our study highlights unexpected instructive role modulating reveals mechanical branch regulatory network. Senescent accumulate aging exhibit enlargement, function which has been unclear decades. Here, authors identify antagonistic genetic circuit hypertrophy reveal SASP.

Язык: Английский

Autophagy-dependent changes in alternative splicing bias translation toward inflammation in senescent cells

Developmental Cell, Год журнала: 2025, Номер 60(3), С. 337 - 339

Опубликована: Фев. 1, 2025

Язык: Английский