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

Preliminary Data on the Senolytic Effects of Agrimonia pilosa Ledeb. Extract Containing Agrimols for Immunosenescence in Middle-Aged Humans: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Comparison Study

Nutrients, Год журнала: 2025, Номер 17(4), С. 667 - 667

Опубликована: Фев. 13, 2025

To assess the effects of agrimol-containing Agrimonia pilosa Ledeb. extract (APE) for senescent immune cell removal in middle-aged Japanese adults with immunosenescence. A randomized, double-blind, placebo-controlled, parallel-group study was conducted Japan between June 2023 and April 2024. 110 individuals aged 40-59, selected based on CD8+ T cells highly-expressing-senescence-associated-β-galactosidase (SA-βGal). Participants were randomly assigned to receive 50 mg APE containing 0.2 agrimols or a placebo eight consecutive weeks. The primary endpoint change proportion high SA-βGal expression at 8 weeks intake from baseline. secondary endpoints included CD4+ expression, subsets, ratio various cells. Of 635 subjects screened, immunosenescence this study. In total, 55 participants group 53 completed intervention. There no statistically significant changes either due intake. male population, reduced by (p = 0.044). Furthermore, naïve increased number effector memory decreased consumption APE. suggested reduce cells, indicating its potential as candidate senolytic agent humans; however, results are preliminary data, further research is needed (clinical trial registration: UMIN000051574).

Язык: Английский

Autophagy-dependent splicing control directs translation toward inflammation during senescence

Developmental Cell, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Язык: Английский