Mitochondria hyperfusion and elevated autophagic activity are key mechanisms for cellular bioenergetic preservation in centenarians.

open17noThe research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2011) under grant agreement n. 259679 (IDEAL), MiUR Prin 2009, and Programma operativo nazionale ricerca e competitività - 2007/2013 PON01_00937 to CF; from Roberto and Cornelia Pallotti Legacy for cancer research to SS and MC; from the Ministry of Education, University and Research (Rome, Italy), the Ministry of Health (Ricerca Finalizzata 2010), the Italian Association for Cancer Research (IG 11505n), Peretti Foundation and Arcobaleno Onlus to WM.Mitochondria have been considered for long time as important determinants of cell aging because of their role in the production of reactive oxygen species. In this study we investigated the impact of mitochondrial metabolism and biology as determinants of successful aging in primary cultures of fibroblasts isolated from the skin of long living individuals (LLI) (about 100 years old) compared with those from young (about 27 years old) and old (about 75 years old) subjects. We observed that fibroblasts from LLI displayed significantly lower complex I-driven ATP synthesis and higher production of H2O2 in comparison with old subjects. Despite these changes, bioenergetics of these cells appeared to operate normally. This lack of functional consequences was likely due to a compensatory phenomenon at the level of mitochondria, which displayed a maintained supercomplexes organization and an increased mass. This appears to be due to a decreased mitophagy, induced by hyperfused, elongated mitochondria. The overall data indicate that longevity is characterized by a preserved bioenergetic function likely attained by a successful mitochondria remodeling that can compensate for functional defects through an increase in mass, i.e. a sort of mitochondrial "hypertrophy".openSgarbi G; Matarrese P; Pinti M; Lanzarini C; Ascione B; Gibellini L; Dika E; Patrizi A; Tommasino C; Capri M; Cossarizza A; Baracca A; Lenaz G; Solaini G; Franceschi C; Malorni W; Salvioli S.Sgarbi G; Matarrese P; Pinti M; Lanzarini C; Ascione B; Gibellini L; Dika E; Patrizi A; Tommasino C; Capri M; Cossarizza A; Baracca A; Lenaz G; Solaini G; Franceschi C; Malorni W; Salvioli S