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 language | English |
|---|---|
| Pages (from-to) | 296-310 |
| Number of pages | 15 |
| Journal | Aging |
| Volume | 6 |
| Issue number | 4 |
| Publication status | Published - 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
Mitochondria hyperfusion and elevated autophagic activity are key mechanisms for cellular bioenergetic preservation in centenarians. / Sgarbi, Gianluca; Matarrese, Paola; Pinti, Marcello; Lanzarini, Catia; Ascione, Barbara; Gibellini, Lara; Dika, Emi; Patrizi, Annalisa; Tommasino, Chiara; Capri, Miriam; Cossarizza, Andrea; Baracca, Alessandra; Lenaz, Giorgio; Solaini, Giancarlo; Franceschi, Claudio; Malorni, Walter; Salvioli, Stefano.
In: Aging, Vol. 6, No. 4, 2014, p. 296-310.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mitochondria hyperfusion and elevated autophagic activity are key mechanisms for cellular bioenergetic preservation in centenarians
AU - Sgarbi, Gianluca
AU - Matarrese, Paola
AU - Pinti, Marcello
AU - Lanzarini, Catia
AU - Ascione, Barbara
AU - Gibellini, Lara
AU - Dika, Emi
AU - Patrizi, Annalisa
AU - Tommasino, Chiara
AU - Capri, Miriam
AU - Cossarizza, Andrea
AU - Baracca, Alessandra
AU - Lenaz, Giorgio
AU - Solaini, Giancarlo
AU - Franceschi, Claudio
AU - Malorni, Walter
AU - Salvioli, Stefano
PY - 2014
Y1 - 2014
N2 - 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".
AB - 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".
KW - Bioenergetics, autophagy, mitophagy
KW - Human aging, longevity
KW - Mitochondria
KW - Reactive oxygen species, dermal fibroblasts
UR - http://www.scopus.com/inward/record.url?scp=84900477487&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84900477487&partnerID=8YFLogxK
M3 - Article
C2 - 24799450
AN - SCOPUS:84900477487
VL - 6
SP - 296
EP - 310
JO - Aging
JF - Aging
SN - 1945-4589
IS - 4
ER -