title: Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents.
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.
authors.affiliation: Laboratory for Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Dongryeol
authors.identifier: 0000-0001-5905-6760
authors.initials: D
authors.lastname: Ryu
authors.affiliation: Laboratory for Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Laurent
authors.initials: L
authors.lastname: Mouchiroud
authors.affiliation: 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.
authors.forename: Pénélope A
authors.initials: PA
authors.lastname: Andreux
authors.affiliation: Laboratory for Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Elena
authors.initials: E
authors.lastname: Katsyuba
authors.affiliation: Laboratory for Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Norman
authors.initials: N
authors.lastname: Moullan
authors.affiliation: Laboratory for Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Amandine A
authors.initials: AA
authors.lastname: Nicolet-Dit-Félix
authors.affiliation: Laboratory for Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Evan G
authors.initials: EG
authors.lastname: Williams
authors.affiliation: Laboratory for Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Pooja
authors.initials: P
authors.lastname: Jha
authors.affiliation: Laboratory for Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lo Sasso
authors.affiliation: Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Damien
authors.initials: D
authors.lastname: Huzard
authors.affiliation: Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Aebischer
authors.affiliation: Laboratory of Behavioral Genetics, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Carmen
authors.initials: C
authors.lastname: Sandi
authors.affiliation: Amazentis SA, Ecole Polytechnique Fédérale de Lausanne Innovation Park, Batiment C, Lausanne, Switzerland.
authors.forename: Chris
authors.initials: C
authors.lastname: Rinsch
authors.affiliation: Laboratory for Integrative and Systems Physiology, Interfaculty Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Johan
authors.initials: J
authors.lastname: Auwerx
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D003374:Coumarins / Q000494:pharmacology*; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000378:metabolism; D005298:Fertility / Q000187:drug effects; D008136:Longevity / Q000187:drug effects*; D051379:Mice; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D063306:Mitophagy / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D032446:Myoblasts / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption; D010614:Pharynx / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D003374:Coumarins; D004272:DNA, Mitochondrial; D012333:RNA, Messenger; C026423:3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one