Publications

Dernière publication 31/03/2026

Homoharringtonine exhibits senotherapeutic activity that mitigates diet- and age

The accumulation of senescent cells in white adipose tissue (WAT) is closely associated with the functional decline of WAT and plays a causal role...

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    [title] => Homoharringtonine exhibits senotherapeutic activity that mitigates diet- and age
    [paragraph] => Homoharringtonine exhibits senotherapeutic activity that mitigates diet- and age-associated obesity and insulin resistance and extends lifespan in mice
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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)
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Une méthode simple pour quantifier objectivement la force musculaire des rats et souris et l'effet de drogues, toxines, maladies musculaires (ex: myopathie) et neurodégénératives. Cette mesure de force est souvent employée en association avec le test de coordination motrice ROTAROD: un sujet présentant une coordination normale montrera des résultats médiocres en cas de faible force musculaire. Un must pour vos recherches sur l'activité, la coordination et le contrôle musculaire: particulièrement utile pour vos études sur les maladies de Parkinson et Huntington.
Nouveautés GS4 - 2023: Écran couleur rétroéclairé (meilleure lisibilité), pédale de remise à zéro, durée de batterie optimisée, taille de mémoire augmentée à 500 valeurs, compteur d'animaux, port USB (transfert de données/charge)

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