Homoharringtonine exhibits senotherapeutic activity that mitigates diet- and age-associated obesity and insulin resistance and extends lifespan in mice

Authors
Kim, Eok-Cheon, Jung, Han-Byul, Park, Yu-kyoung, Son, Youlim, Cha, Hye-Na, Patel, Yash, Lee, Ju Hee, Choi, Minah, Park, Soyoung, Kim, Il-Kug, Pickel, Lauren, Lee, Seungju, Ha, Yuna, Shin, Min-Gyeong, Zhang, Qiwei, Yang, Jielin, de Oliveira, Bruno Rodrigues, Vo, Nathaniel, Yew, Annie, Togo, Jacques, Ealey, Kafi N., Jung, Su-Ryun, Moon, Sunjin, Yoon, Hye-Jin, Lee, Jee-Young, Sung, Hoon-Ki, Kim, Jae-Ryong, Park, So-Young


Lab

Journal
Nature Communications

Abstract
The accumulation of senescent cells in white adipose tissue (WAT) is closely associated with the functional decline of WAT and plays a causal role in the pathogenesis of metabolic diseases. Therefore, the elimination of senescent cells in WAT holds promise for the treatment and prevention of age-related metabolic diseases. Using a drug-repositioning strategy for 2150 clinically applied compounds, we discover that homoharringtonine (HHT), an FDA-approved anti-leukemic drug, manifests senotherapeutic activity in vitro in multiple cell types including human preadipocytes, while inflicting minimal cytotoxicity to non-senescent cells. HHT treatment prevents diet- or age-induced metabolic abnormalities in male mice targeting senescent adipocytes and preadipocytes to improve WAT function and reduce WAT inflammation. Moreover, HHT treatment attenuates age-associated phenotypes of human adipose tissue. Mechanistically, the senotherapeutic effects of HHT are mediated through the direct interaction of HHT with heat shock protein family A member 5 (HSPA5). Importantly, we found that HHT treatment delays aging and extends the lifespan in progeroid and aged mice. Our study demonstrates the novel senotherapeutic potential of HHT to mitigate age- and obesity-related metabolic dysfunction and extend longevity in mice. This study identifies an FDA-approved leukemia drug, Homoharringtonine, that can eliminate aged fat cells, improve metabolic health, reduce inflammation and extend lifespan in mice, revealing a potential approach to treat age- and obesity-related metabolic disease.

Keywords/Topics
Molecular medicine; Obesity; Phenotypic screening; Senescence

BIOSEB Instruments Used:
Grip strength test (BIO-GS4)

Source :

https://www.nature.com/articles/s41467-026-70475-3

Produits associés

Test d'agrippement

DEMANDE DE PUBLICATION

Merci de votre intérêt pour notre gamme de produits et de votre demande pour cette publication qui vous sera envoyée si l'équipe de recherche et la revue le permettent. Notre équipe commerciale vous contactera dans les plus brefs délais.