Study of the role of mitochondria and the mitochondrial genetic system in the aging process and in age-related pathological conditions (sarcopenia, diabetes, neurodegenerative diseases, cancer etc) as well as of the nutritional strategies or drugs that may prevent the degenerative processes, eventually promoting mitochondrial biogenesis and dynamics. Study of nuclear factors involved in the signaling pathways of mitochondrial biogenesis (PGC1s, Akt, SIRTs) and dynamics. Determination and quantification of mtDNA damages, as well as analysis of mtDNA stability and TFAM-mtDNA interactions. Experimental models are: i) tissue samples from rats and humans of different ages (collaboration with Prof. E. Marzetti, Univ. Cattolica - Sacro Cuore, Roma), ii) rats treated with caloric restriction diet (collaboration with Prof. C. Leeuwenburgh, Univ. of Florida, Gainesville, FL, USA and Prof. A. Picca, Department of Medicine and Surgery, LUM University, Casamassima, Bari), compounds qualified as nutraceuticals or drugs iii) cancer tissues samples. Studies on pathogenetic mechanisms responsible for the Leber Hereditary Optic Neuropathy. Role of mitochondrial biogenesis in modulating the disease penetrance and as predictive tool for the clinical manifestation of the disease. Studies on mitochondrial tRNA related diseases (MELAS and MERRF): evaluation of tissue-specific effects and rescuing mechanisms of therapeutic molecules derived from mitochondrial leucyl tRNA synthetase (collaboration with prof. G. d’Amati, Università La Sapienza, Roma). Study of mitochondrial DNA replication and transcription machinery in animal systems, aimed at the identification and characterization of new regulatory factors/enzymes (collaboration with prof. N.G. Larsson, Dept of Med. Biochem. and Biophys., Karolinska Institutet, Stockholm, Sweden). Different publications identifies Mgme1 exonuclease as a crucial regulator of mitochondrial DNA replication, as shown by mitochondrial pathologies caused by mutations in this gene.