Advancements in therapeutic drugs targeting of senescence DOI

Mingsheng Zhu,

Ping Meng,

Xian Ling

et al.

Therapeutic Advances in Chronic Disease, Journal Year: 2020, Volume and Issue: 11

Published: Jan. 1, 2020

Aging leads to a high burden on society, both medically and economically. Cellular senescence plays an essential role in the initiation of aging age-related diseases. Recent studies have highlighted therapeutic value senescent cell deletion natural many disorders. However, strategies for manipulating cellular are still at early stage development. Among these strategies, drugs that target arguably most highly anticipated. Many recent demonstrated variety exhibit healthy effects. In this review, we summarize different types promoting - such as senolytics, senescence-associated secretory phenotype (SASP) inhibitors, nutrient signaling regulators provide update their potential merits. Taken together, our review synthesizes advancements potentialities with regard clinical implications.

Language: Английский

Senescent-like macrophages mediate angiogenesis for endplate sclerosis via IL-10 secretion in male mice DOI Creative Commons
Yonggang Fan, Weixin Zhang,

Xiusheng Huang

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 5, 2024

Abstract Endplate sclerosis is a notable aspect of spine degeneration or aging, but the mechanisms remain unclear. Here, we report that senescent macrophages accumulate in sclerotic endplates lumbar instability (LSI) aging male mouse model. Specifically, knockout cdkn2a (p16) abrogates LSI aging-induced angiogenesis and endplates. Furthermore, both vivo vitro studies indicate IL-10 primary elevated cytokine senescence-related secretory phenotype (SASP). Mechanistically, increases pSTAT3 endothelial cells, leading to directly binding promoters Vegfa, Mmp2, Pdgfb encourage their production, resulting angiogenesis. This study provides information on understanding link between immune senescence endplate sclerosis, which might be useful for therapeutic approaches.

Language: Английский

Citations

10
Cell enlargement modulated by GATA4 and YAP instructs the senescence-associated secretory phenotype DOI Creative Commons

J. P. W. Joung,

Y.‐A. Heo,

Yeonju Kim

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 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.

Language: Английский

Citations

1
The PTEN Conundrum: How to Target PTEN-Deficient Prostate Cancer DOI Creative Commons
Daniel J. Turnham, Nicholas Bullock,

Manisha S. Dass

et al.

Cells, Journal Year: 2020, Volume and Issue: 9(11), P. 2342 - 2342

Published: Oct. 22, 2020

Loss of the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN), which negatively regulates PI3K–AKT–mTOR pathway, is strongly linked to advanced prostate cancer progression poor clinical outcome. Accordingly, several therapeutic approaches are currently being explored combat PTEN-deficient tumors. These include classical inhibition signaling network, as well new that restore PTEN function, or target regulation stability, DNA damage repair microenvironment. While targeting remains a challenge, advances in field precision medicine indicate loss provides valuable biomarker stratify patients for treatments, may improve overall Here, we discuss implications management review recent cancer. Deepening our understanding how contributes growth resistance will inform design future studies precision-medicine strategies ultimately patient care.

Language: Английский

Citations

62
Coordinate regulation of the senescent state by selective autophagy DOI Creative Commons
Yeonghyeon Lee, Jaejin Kim,

Mi-Sung Kim

et al.

Developmental Cell, Journal Year: 2021, Volume and Issue: 56(10), P. 1512 - 1525.e7

Published: April 28, 2021

Language: Английский

Citations

55
Advancements in therapeutic drugs targeting of senescence DOI

Mingsheng Zhu,

Ping Meng,

Xian Ling

et al.

Therapeutic Advances in Chronic Disease, Journal Year: 2020, Volume and Issue: 11

Published: Jan. 1, 2020

Aging leads to a high burden on society, both medically and economically. Cellular senescence plays an essential role in the initiation of aging age-related diseases. Recent studies have highlighted therapeutic value senescent cell deletion natural many disorders. However, strategies for manipulating cellular are still at early stage development. Among these strategies, drugs that target arguably most highly anticipated. Many recent demonstrated variety exhibit healthy effects. In this review, we summarize different types promoting - such as senolytics, senescence-associated secretory phenotype (SASP) inhibitors, nutrient signaling regulators provide update their potential merits. Taken together, our review synthesizes advancements potentialities with regard clinical implications.

Language: Английский

Citations

51