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

Gianluca Sgarbi, Paola Matarrese, Marcello Pinti, Catia Lanzarini, Barbara Ascione, Lara Gibellini, Emi Dika, Annalisa Patrizi, Chiara Tommasino, Miriam Capri, Andrea Cossarizza, Alessandra Baracca, Giorgio Lenaz, Giancarlo Solaini, Claudio Franceschi, Walter Malorni, Stefano Salvioli

Research output: Contribution to journalArticle

Abstract

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".

Original languageEnglish
Pages (from-to)296-310
Number of pages15
JournalAging
Volume6
Issue number4
Publication statusPublished - 2014

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Keywords

  • Bioenergetics, autophagy, mitophagy
  • Human aging, longevity
  • Mitochondria
  • Reactive oxygen species, dermal fibroblasts

ASJC Scopus subject areas

  • Ageing
  • Cell Biology
  • Medicine(all)

Cite this

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. (2014). Mitochondria hyperfusion and elevated autophagic activity are key mechanisms for cellular bioenergetic preservation in centenarians. Aging, 6(4), 296-310.