Luis Filipe Costa-Machado, Esther Garcia-Dominguez, Rebecca L McIntyre, Jose Luis Lopez-Aceituno, Álvaro Ballesteros-Gonzalez, Andrea Tapia-Gonzalez, David Fabregat-Safont, Tobias Eisenberg, Jesús Gomez, Adrian Plaza, Aranzazu Sierra-Ramirez, Manuel Perez, David Villanueva-Bermejo, Tiziana Fornari, María Isabel Loza, Gonzalo Herradon, Sebastian J Hofer, Christoph Magnes, Frank Madeo, Janet S Duerr, Oscar J Pozo, Maximo-Ibo Galindo, Isabel Del Pino, Riekelt H Houtkooper, Diego Megias, Jose Viña, Mari Carmen Gomez-Cabrera, Pablo J Fernandez-Marcos
Reversible and sub-lethal stresses to the mitochondria elicit a program of compensatory responses that ultimately improve mitochondrial function, a conserved anti-aging mechanism termed mitohormesis. Here, we show that harmol, a member of the beta-carbolines family with anti-depressant properties, improves mitochondrial function and metabolic parameters, and extends healthspan. Treatment with harmol induces a transient mitochondrial depolarization, a strong mitophagy response, and the AMPK compensatory pathway both in cultured C2C12 myotubes and in male mouse liver, brown adipose tissue and muscle, even though harmol crosses poorly the blood-brain barrier...
May 15, 2023: Nature Communications