Older Adults with Physical Frailty and Sarcopenia Show Increased Levels of Circulating Small Extracellular Vesicles with a Specific Mitochondrial Signature
Mitochondrial dysfunction and systemic inflammation are major factors in the development of sarcopenia, but the molecular determinants linking the two mechanisms are only partially understood. The study of extracellular vesicle (EV) trafficking may provide insights into this relationship. Circulatin...
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| Format: | Article |
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MDPI AG
2020-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/4/973 |
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| author | Anna Picca Raffaella Beli Riccardo Calvani Hélio José Coelho-Júnior Francesco Landi Roberto Bernabei Cecilia Bucci Flora Guerra Emanuele Marzetti |
| author_facet | Anna Picca Raffaella Beli Riccardo Calvani Hélio José Coelho-Júnior Francesco Landi Roberto Bernabei Cecilia Bucci Flora Guerra Emanuele Marzetti |
| author_sort | Anna Picca |
| collection | DOAJ |
| description | Mitochondrial dysfunction and systemic inflammation are major factors in the development of sarcopenia, but the molecular determinants linking the two mechanisms are only partially understood. The study of extracellular vesicle (EV) trafficking may provide insights into this relationship. Circulating small EVs (sEVs) from serum of 11 older adults with physical frailty and sarcopenia (PF&S) and 10 controls were purified and characterized. Protein levels of three tetraspanins (CD9, CD63, and CD81) and selected mitochondrial markers, including adenosine triphosphate 5A (ATP5A), mitochondrial cytochrome C oxidase subunit I (MTCOI), nicotinamide adenine dinucleotide reduced form (NADH):ubiquinone oxidoreductase subunit B8 (NDUFB8), NADH:ubiquinone oxidoreductase subunit S3 (NDUFS3), succinate dehydrogenase complex iron sulfur subunit B (SDHB), and ubiquinol-cytochrome C reductase core protein 2 (UQCRC2) were quantified by Western immunoblotting. Participants with PF&S showed higher levels of circulating sEVs relative to controls. Protein levels of CD9 and CD63 were lower in the sEV fraction of PF&S older adults, while CD81 was unvaried between groups. In addition, circulating sEVs from PF&S participants had lower amounts of ATP5A, NDUFS3, and SDHB. No signal was detected for MTCOI, NDUFB8, or UQCRC2 in either participant group. Our findings indicate that, in spite of increased sEV secretion, lower amounts of mitochondrial components are discarded through EV in older adults with PF&S. In-depth analysis of EV trafficking might open new venues for biomarker discovery and treatment development for PF&S. |
| first_indexed | 2024-03-10T20:28:15Z |
| format | Article |
| id | doaj.art-857bbc4dafff4dafbf4969aac14bd7a6 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T20:28:15Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-857bbc4dafff4dafbf4969aac14bd7a62023-11-19T21:39:01ZengMDPI AGCells2073-44092020-04-019497310.3390/cells9040973Older Adults with Physical Frailty and Sarcopenia Show Increased Levels of Circulating Small Extracellular Vesicles with a Specific Mitochondrial SignatureAnna Picca0Raffaella Beli1Riccardo Calvani2Hélio José Coelho-Júnior3Francesco Landi4Roberto Bernabei5Cecilia Bucci6Flora Guerra7Emanuele Marzetti8Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, ItalyDepartment of Biological and Environmental Sciences and Technologies, Università del Salento, 73100 Lecce, ItalyFondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, ItalyUniversità Cattolica del Sacro Cuore, 00168 Rome, ItalyFondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, ItalyFondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, ItalyDepartment of Biological and Environmental Sciences and Technologies, Università del Salento, 73100 Lecce, ItalyDepartment of Biological and Environmental Sciences and Technologies, Università del Salento, 73100 Lecce, ItalyFondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, ItalyMitochondrial dysfunction and systemic inflammation are major factors in the development of sarcopenia, but the molecular determinants linking the two mechanisms are only partially understood. The study of extracellular vesicle (EV) trafficking may provide insights into this relationship. Circulating small EVs (sEVs) from serum of 11 older adults with physical frailty and sarcopenia (PF&S) and 10 controls were purified and characterized. Protein levels of three tetraspanins (CD9, CD63, and CD81) and selected mitochondrial markers, including adenosine triphosphate 5A (ATP5A), mitochondrial cytochrome C oxidase subunit I (MTCOI), nicotinamide adenine dinucleotide reduced form (NADH):ubiquinone oxidoreductase subunit B8 (NDUFB8), NADH:ubiquinone oxidoreductase subunit S3 (NDUFS3), succinate dehydrogenase complex iron sulfur subunit B (SDHB), and ubiquinol-cytochrome C reductase core protein 2 (UQCRC2) were quantified by Western immunoblotting. Participants with PF&S showed higher levels of circulating sEVs relative to controls. Protein levels of CD9 and CD63 were lower in the sEV fraction of PF&S older adults, while CD81 was unvaried between groups. In addition, circulating sEVs from PF&S participants had lower amounts of ATP5A, NDUFS3, and SDHB. No signal was detected for MTCOI, NDUFB8, or UQCRC2 in either participant group. Our findings indicate that, in spite of increased sEV secretion, lower amounts of mitochondrial components are discarded through EV in older adults with PF&S. In-depth analysis of EV trafficking might open new venues for biomarker discovery and treatment development for PF&S.https://www.mdpi.com/2073-4409/9/4/973agingbiomarkersmitophagymitochondrial dynamicsmitochondrial quality controlmitochondrial-derived vesicles (MDVs) |
| spellingShingle | Anna Picca Raffaella Beli Riccardo Calvani Hélio José Coelho-Júnior Francesco Landi Roberto Bernabei Cecilia Bucci Flora Guerra Emanuele Marzetti Older Adults with Physical Frailty and Sarcopenia Show Increased Levels of Circulating Small Extracellular Vesicles with a Specific Mitochondrial Signature Cells aging biomarkers mitophagy mitochondrial dynamics mitochondrial quality control mitochondrial-derived vesicles (MDVs) |
| title | Older Adults with Physical Frailty and Sarcopenia Show Increased Levels of Circulating Small Extracellular Vesicles with a Specific Mitochondrial Signature |
| title_full | Older Adults with Physical Frailty and Sarcopenia Show Increased Levels of Circulating Small Extracellular Vesicles with a Specific Mitochondrial Signature |
| title_fullStr | Older Adults with Physical Frailty and Sarcopenia Show Increased Levels of Circulating Small Extracellular Vesicles with a Specific Mitochondrial Signature |
| title_full_unstemmed | Older Adults with Physical Frailty and Sarcopenia Show Increased Levels of Circulating Small Extracellular Vesicles with a Specific Mitochondrial Signature |
| title_short | Older Adults with Physical Frailty and Sarcopenia Show Increased Levels of Circulating Small Extracellular Vesicles with a Specific Mitochondrial Signature |
| title_sort | older adults with physical frailty and sarcopenia show increased levels of circulating small extracellular vesicles with a specific mitochondrial signature |
| topic | aging biomarkers mitophagy mitochondrial dynamics mitochondrial quality control mitochondrial-derived vesicles (MDVs) |
| url | https://www.mdpi.com/2073-4409/9/4/973 |
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