Cargando…

Anti-aging effects of chlorpropamide depend on mitochondrial complex-II and the production of mitochondrial reactive oxygen species

Sulfonylureas are widely used oral anti-diabetic drugs. However, its long-term usage effects on patients’ lifespan remain controversial, with no reports of influence on animal longevity. Hence, the anti-aging effects of chlorpropamide along with glimepiride, glibenclamide, and tolbutamide were studi...

Descripción completa

Detalles Bibliográficos
Autores principales: Mao, Zhifan, Liu, Wenwen, Huang, Yunyuan, Sun, Tianyue, Bao, Keting, Feng, Jiali, Moskalev, Alexey, Hu, Zelan, Li, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8897034/
https://www.ncbi.nlm.nih.gov/pubmed/35256938
http://dx.doi.org/10.1016/j.apsb.2021.08.007
_version_ 1784663304556249088
author Mao, Zhifan
Liu, Wenwen
Huang, Yunyuan
Sun, Tianyue
Bao, Keting
Feng, Jiali
Moskalev, Alexey
Hu, Zelan
Li, Jian
author_facet Mao, Zhifan
Liu, Wenwen
Huang, Yunyuan
Sun, Tianyue
Bao, Keting
Feng, Jiali
Moskalev, Alexey
Hu, Zelan
Li, Jian
author_sort Mao, Zhifan
collection PubMed
description Sulfonylureas are widely used oral anti-diabetic drugs. However, its long-term usage effects on patients’ lifespan remain controversial, with no reports of influence on animal longevity. Hence, the anti-aging effects of chlorpropamide along with glimepiride, glibenclamide, and tolbutamide were studied with special emphasis on the interaction of chlorpropamide with mitochondrial ATP-sensitive K(+) (mitoK-ATP) channels and mitochondrial complex II. Chlorpropamide delayed aging in Caenorhabditis elegans, human lung fibroblast MRC-5 cells and reduced doxorubicin-induced senescence in both MRC-5 cells and mice. In addition, the mitochondrial membrane potential and ATP levels were significantly increased in chlorpropamide-treated worms, which is consistent with the function of its reported targets, mitoK-ATP channels. Increased levels of mitochondrial reactive oxygen species (mtROS) were observed in chlorpropamide-treated worms. Moreover, the lifespan extension by chlorpropamide required complex II and increased mtROS levels, indicating that chlorpropamide acts on complex II directly or indirectly via mitoK-ATP to increase the production of mtROS as a pro-longevity signal. This study provides mechanistic insight into the anti-aging effects of sulfonylureas in C. elegans.
format Online
Article
Text
id pubmed-8897034
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-88970342022-03-06 Anti-aging effects of chlorpropamide depend on mitochondrial complex-II and the production of mitochondrial reactive oxygen species Mao, Zhifan Liu, Wenwen Huang, Yunyuan Sun, Tianyue Bao, Keting Feng, Jiali Moskalev, Alexey Hu, Zelan Li, Jian Acta Pharm Sin B Original Article Sulfonylureas are widely used oral anti-diabetic drugs. However, its long-term usage effects on patients’ lifespan remain controversial, with no reports of influence on animal longevity. Hence, the anti-aging effects of chlorpropamide along with glimepiride, glibenclamide, and tolbutamide were studied with special emphasis on the interaction of chlorpropamide with mitochondrial ATP-sensitive K(+) (mitoK-ATP) channels and mitochondrial complex II. Chlorpropamide delayed aging in Caenorhabditis elegans, human lung fibroblast MRC-5 cells and reduced doxorubicin-induced senescence in both MRC-5 cells and mice. In addition, the mitochondrial membrane potential and ATP levels were significantly increased in chlorpropamide-treated worms, which is consistent with the function of its reported targets, mitoK-ATP channels. Increased levels of mitochondrial reactive oxygen species (mtROS) were observed in chlorpropamide-treated worms. Moreover, the lifespan extension by chlorpropamide required complex II and increased mtROS levels, indicating that chlorpropamide acts on complex II directly or indirectly via mitoK-ATP to increase the production of mtROS as a pro-longevity signal. This study provides mechanistic insight into the anti-aging effects of sulfonylureas in C. elegans. Elsevier 2022-02 2021-08-10 /pmc/articles/PMC8897034/ /pubmed/35256938 http://dx.doi.org/10.1016/j.apsb.2021.08.007 Text en © 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Mao, Zhifan
Liu, Wenwen
Huang, Yunyuan
Sun, Tianyue
Bao, Keting
Feng, Jiali
Moskalev, Alexey
Hu, Zelan
Li, Jian
Anti-aging effects of chlorpropamide depend on mitochondrial complex-II and the production of mitochondrial reactive oxygen species
title Anti-aging effects of chlorpropamide depend on mitochondrial complex-II and the production of mitochondrial reactive oxygen species
title_full Anti-aging effects of chlorpropamide depend on mitochondrial complex-II and the production of mitochondrial reactive oxygen species
title_fullStr Anti-aging effects of chlorpropamide depend on mitochondrial complex-II and the production of mitochondrial reactive oxygen species
title_full_unstemmed Anti-aging effects of chlorpropamide depend on mitochondrial complex-II and the production of mitochondrial reactive oxygen species
title_short Anti-aging effects of chlorpropamide depend on mitochondrial complex-II and the production of mitochondrial reactive oxygen species
title_sort anti-aging effects of chlorpropamide depend on mitochondrial complex-ii and the production of mitochondrial reactive oxygen species
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8897034/
https://www.ncbi.nlm.nih.gov/pubmed/35256938
http://dx.doi.org/10.1016/j.apsb.2021.08.007
work_keys_str_mv AT maozhifan antiagingeffectsofchlorpropamidedependonmitochondrialcomplexiiandtheproductionofmitochondrialreactiveoxygenspecies
AT liuwenwen antiagingeffectsofchlorpropamidedependonmitochondrialcomplexiiandtheproductionofmitochondrialreactiveoxygenspecies
AT huangyunyuan antiagingeffectsofchlorpropamidedependonmitochondrialcomplexiiandtheproductionofmitochondrialreactiveoxygenspecies
AT suntianyue antiagingeffectsofchlorpropamidedependonmitochondrialcomplexiiandtheproductionofmitochondrialreactiveoxygenspecies
AT baoketing antiagingeffectsofchlorpropamidedependonmitochondrialcomplexiiandtheproductionofmitochondrialreactiveoxygenspecies
AT fengjiali antiagingeffectsofchlorpropamidedependonmitochondrialcomplexiiandtheproductionofmitochondrialreactiveoxygenspecies
AT moskalevalexey antiagingeffectsofchlorpropamidedependonmitochondrialcomplexiiandtheproductionofmitochondrialreactiveoxygenspecies
AT huzelan antiagingeffectsofchlorpropamidedependonmitochondrialcomplexiiandtheproductionofmitochondrialreactiveoxygenspecies
AT lijian antiagingeffectsofchlorpropamidedependonmitochondrialcomplexiiandtheproductionofmitochondrialreactiveoxygenspecies