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PMID: 27400265 Published · ppublish English Journal Article

Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents.

Nature medicine ·Vol. 22 ·No. 8 ·2016-00-00 ·Pages 879-88

Ryu D, Mouchiroud L, Andreux PA, Katsyuba E, Moullan N, Nicolet-Dit-Félix AA, Williams EG, Jha P, Lo Sasso G, Huzard D, Aebischer P, Sandi C, Rinsch C, Auwerx J

Abstract

The biological effects of urolithins remain poorly characterized, despite wide-spread human exposure via the dietary consumption of their metabolic precursors, the ellagitannins, which are found in the pomegranate fruit, as well as in nuts and berries. We identified urolithin A (UA) as a first-in-class natural compound that induces mitophagy both in vitro and in vivo following oral consumption. In C. elegans, UA prevented the accumulation of dysfunctional mitochondria with age and extended lifespan. Likewise, UA prolonged normal activity during aging in C. elegans, including mobility and pharyngeal pumping, while maintaining mitochondrial respiratory capacity. These effects translated to rodents, where UA improved exercise capacity in two different mouse models of age-related decline of muscle function, as well as in young rats. Our findings highlight the health benefits of urolithin A and its potential application in strategies to improve mitochondrial and muscle function.

MeSH Terms
Animals Caenorhabditis elegans Coumarins/pharmacology DNA, Mitochondrial/drug effects,metabolism Fertility/drug effects Longevity/drug effects Mice Microscopy, Confocal Mitochondria/drug effects,metabolism Mitophagy/drug effects Muscle, Skeletal/drug effects,metabolism Myoblasts/drug effects,metabolism Oxygen Consumption Pharynx/drug effects RNA, Messenger/drug effects,metabolism Rats Real-Time Polymerase Chain Reaction
Chemicals
Coumarins DNA, Mitochondrial RNA, Messenger 3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Ryu Dongryeol ORCID
Laboratory for Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Mouchiroud Laurent
Laboratory for Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Andreux Pénélope A
Laboratory for Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. | Amazentis SA, Ecole Polytechnique Fédérale de Lausanne Innovation Park, Batiment C, Lausanne, Switzerland.
Katsyuba Elena
Laboratory for Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Moullan Norman
Laboratory for Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Nicolet-Dit-Félix Amandine A
Laboratory for Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Williams Evan G
Laboratory for Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Jha Pooja
Laboratory for Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Lo Sasso Giuseppe
Laboratory for Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Huzard Damien
Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Aebischer Patrick
Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Sandi Carmen
Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Rinsch Chris
Amazentis SA, Ecole Polytechnique Fédérale de Lausanne Innovation Park, Batiment C, Lausanne, Switzerland.
Auwerx Johan
Laboratory for Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
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Article Info
Journal
Nature medicine
Abbr.
Nat Med
ISSN
1546-170X
DOI
10.1038/nm.4132
Published
2016-00-00
Epub
2016-00-11
Pages
879-88
Language
English
Region
United States
NLM ID
9502015
Subset
IM
External Links
PubMed source DOI: 10.1038/nm.4132 View journal details
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