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Mitochondria, metabolism, and longevity: new drugs and precision nutrition (Nisoli’s Lab)  

General description
The Nisoli Lab at the Biometra Department studies the molecular pathophysiology of non-communicable disorders to identify innovative drug and nutritional therapies. In particular, we investigate the role of mitochondria in metabolic syndrome, obesity, type 2 diabetes, and cardiovascular disease. For the past 20 years, our lab has made important contributions to the burgeoning field of nutrient metabolism and mitochondria, demonstrating the role of nitric oxide (NO) system as a drug target. We have shown that this regulatory system plays an essential role in health span extension promoted by calorie restriction. Induction of mitochondrial biogenesis in metabolically active tissues, in particular adipose tissue, is primarily involved. These mechanistic results have been confirmed by multiple groups, as well as proteomics approaches have very recently illuminated fat as the key tissue in ageing.  Based on this previous work, in the last five years, we have created designer amino acid mixtures able to promote NO production and mitochondrial biogenesis. These combinations enhance energy metabolism in ageing and age-related disorders. We have demonstrated that the amino acid supplementation with specific mixtures prolongs the lifespan of mice.
Moreover, we found that these amino acid formulas can ameliorate mitochondrial dysfunction in diverse clinical settings: among others, drug-induced cardiotoxicity, alcohol-dependent liver damage, and genetic Duchenne muscular dystrophy. At present, we are characterizing a new nutritional strategy to healthy affect metabolic dysfunctions – altered glucose and lipid metabolism, defective energy homeostasis, and changed intestinal microbiota – typically observed in obese and diabetic patients, in addition to older adults. The strategy consists in substituting protein component of a diet with amino acid mixtures, specifically designed to improve energy metabolism in single tissue and organs. The overall aim is to identify selective nutrient combinations for single metabolic disorders. 


Research themes
Mitochondrial bioenergetics; nutrient metabolism; amino acid metabolism; nitric oxide; molecular mechanisms of aging; calorie restriction and intermittent fasting; mitochondrial pharmacology; anti-obesity, anti-diabetic, cardiovascular drugs


Clark electrode for the study of oxygen consumption and the metabolic pathways involved in cells and tissues; Biochrom30 + for the quantitative and qualitative determination of amino acids of biological interest


Lab members             
Maurizio Ragni, PhDmaurizio.ragni@unimi.it 
Chiara Ruocco, PhDchiararuocco@gmail.com 
Laura Tedesco, PhDted.laura@libero.it 


Office: +39 02 5031 6956
Laboratory: +39 02 50317116
Email: enzo.nisoli@unimi.it


Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, sede di via Vanvitelli 32, 20129 Milano; Stanza R016, Edificio 32110, Piano Rialzato.


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